What are the differences between cancer and tumour?

What are the differences between cancer and tumour?

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What are the differences between cancer and tumour? I mean is it in the DNA or shape or something else… And how can a benign tumour turn into a malignant tumour? The body has a lot of tumours all the time, however not all of them become cancerous, why is this so?

So my main question is: What is so special about cancer cells that they can get out of control unlike an ordinary benign tumour?

A tumour is simply a space-occupying lesion (something that should not be there, that is; a "lump") caused by abnormal cell replication.

(In medicine, the word "tumour" literally means "swelling", and can sometimes refer to that instead, but that's a different story).

Cancer is a disease in which cell replication is totally out of control. What causes cancer is damage to the genes (DNA) which normally stop cell replication when it needs to be stopped.

There's no such thing as an "ordinary tumour"; all tumours are abnormal. However, what makes a benign (harmless) tumour different from a cancerous tumour is that there is still some mechanisms stopping the cells inside the tumour from replicating; they are doing it more than they should, but they are not totally out of control. When those last mechanisms are broken too, the tumour is cancerous.

(This is a simplified explanation; the actual explanation is a semester-long university course. It's mostly accurate for the layman, though)

Tl;dr answer, tumors are abnormal growth (or swelling, thanks to Malic for pointing out) of any kind. The kinds of tumors are benign and malignant.

Benign tumors are usually slow growing and harmless. Example would be a lipoma.

Malignant tumors are otherwise called cancers. They generally have a bad prognosis. Very few cancers are curable.

Swelling over an injury (which is also called tumor) is due to local transudation (shift of plasma from capillaries). This is temporary and usually goes down one the injury heals.

Benign Tumor vs. Malignant Tumor

The difference between benign and malignant tumors is that a benign tumor does not invade its surrounding structures while a malignant tumor invades its surrounding structures.

A tumor is formed when the uncontrolled division of the cells occurs, and a mass appears in the form of a lump which is termed as a tumor. A tumor may be benign or malignant in nature. A benign tumor is that which does not spread beyond its limit and never invades its surrounding structures. While a malignant tumor is that which invades its surrounding structures and spreads in the body at distant places. The spread of a malignant tumor is termed as metastasis.

Histologically, the benign tumor appears similar to the cells of origin while malignant tumors vary ranging from similar to the cells of origin to totally anaplastic (different). Tumor edges of benign tumors grow outward in a smooth fashion and do not infiltrate to surrounding tissues while tumor edges of malignant tumors grow outward in an irregular fashion and infiltrate the surrounding structures.

Tumor cells of benign tumors do not separate from the clone or mass of cells from which they originated. They remain attached with the clone of cells. They do not metastasize elsewhere in the body. While the tumor cells of malignant tumors detach from the clone or mass of cells of their origin and tend to metastasize in the distant places of the body. This tendency of malignant cells is called as metastasis.

The growth rate of benign tumors is slow while the growth rate of malignant tumors is fast.

Benign tumors have slight vascularity. They have a poor blood supply. While malignant tumors have moderate to the rich blood supply and that is the reason they grow rapidly because they are provided with adequate blood supply required for rapid growth.

Necrosis and ulceration do not occur commonly in benign tumors while necrosis and ulceration are common in the malignant type of tumors.

Benign tumors do not affect the systems of the body unless they secrete any hormone which is less common. While metastatic tumors have adverse systemic effects. They spread to the brain, bones, liver, heart, kidney and other distant areas of the body and have adverse effects on their functions.

Benign tumors are usually encapsulated while malignant tumors are not encapsulated. Due to the presence of a capsule, benign tumors are sharply demarcated while malignant tumors are not demarcated due to their invasion of the surrounding tissues.

There is no history of weight loss in the patients suffering from benign tumors while there is remarkable weight loss in the patients who have advanced stage of malignant tumors.

Benign tumors are not further classified according to their staging while malignant tumors are further classified according to TNM classification to understand the degree of their extent.

Benign tumors of hepatocytes are called hepatocellular adenoma while malignant tumors of hepatic cells are called hepatocellular carcinoma.

Benign tumors of squamous cells of the skin are called squamous cell adenoma while malignant cells of squamous cells are called squamous cells carcinoma.

Loving Biology

Not all cancers are fatal and horrifying. There are generally two main types of tumors, which are benign and malignant.

Benign tumors, also known as non-malignant cells, are a group of cells that grows uncontrollably like malignant tumors. However, benign tumors aren’t very harmful. Benign tumors grow very slowly, taking months or even years to grow significantly. For malignant cells, it takes about few weeks to increase significantly in size. Benign tumors don’t even spread from one tissue or areas of the body to the other. They are enclosed in a protective sac that prevents them from moving around freely and invading to other locations. Malignant tumors, as a contrast, are not enclosed in a protective coating and they move freely around the body, invading other tissues and organs.

Benign tumors are well-circumscribed as well. Well-circumscribed means that the starting and ending of the tumor is evident, which allows doctors to recognize and remove it much more easily. However, malignant tumors rarely are circumscribed, which indicates that it is harder for doctors to find out the origin and ending point of the cancer. Therefore, it is harder to completely remove the malignant cancer tumor as even if a tiny amount of cancer cells are left, they will reproduce rapidly.

As benign tumors are mostly static, they tend to cause no harm to people at all. However, there are several cases where benign tumors can have a negative influence on the person. Firstly, if the benign tumor grew on a vital organ or tissues, such as on a primary nerve, a main artery, and brain nerves, it can cause a serious problem and intolerable pain. Secondly, if the benign tumor develops into the malignant tumor, it will be critical to our body as well. However, such happenings are extremely rare, almost impossible.

Those are the most basic factors that distinguishes benign tumor and malignant tumor.

Benign vs. Malignant Tumors: Understanding the Difference

A tumor is a solid or fluid-filled mass of tissue which can appear almost anywhere in the body. Tumors can be any shape or size, and may be benign or malignant.

The Definition of Benign and Malignant

People often talk about benign and malignant tumors, but what does this mean? The dictionary definition of benign is “not recurrent favorable for recovery with appropriate treatment.”

When talking about tumors, benign means not cancerous or directly threatening to life. It is the opposite of malignant, which is defined as "tending to become progressively worse and to result in death having the properties of anaplasia, invasiveness, and metastasis said of tumors."

This means that cells in malignant tumors can change their structure and travel to other areas of the body. These are the type of tumors which cause cancer, and if left untreated, they may be fatal.

Benign vs. Malignant Tumor Characteristics

Benign Tumors

Benign tumors can affect many different parts of the body including organs, glands, nerves, connective tissue and the skin. They will vary in size and shape depending on where they are and what is causing them.

Benign tumors are often surrounded by a sac which is created by the immune system to keep them separated from the rest of the body. Benign tumors grow slowly, if at all, and cannot spread to other areas.

These tumors are not harmful in themselves but may cause issues such as pain or discomfort if they press against a blood vessel or nerve. Sometimes a benign tumor forms in the endocrine system, on glands such as the pituitary gland or the thyroid. This can cause hormonal imbalances and further, potentially serious symptoms. These symptoms will depend on exactly which glands and hormones are affected.

Malignant Tumors

The immune system is usually very effective at destroying cells which could become cancerous, but sometimes a few slip through the net. These cells can quickly grow into malignant tumors, putting your health at risk.

Malignant tumors are cancerous and can spread to different areas of the body through the blood or lymphatic system. They grow and travel quickly, meaning that early detection is vital if they are to be stopped. These tumors are graded on a scale from 0–4 which is used to indicate their size and how much they have spread.

Like benign tumors, malignant tumors can affect many different areas of the body. Some of the most common are the breasts, testicles, prostate gland, lungs, liver, and stomach.

What Is the Difference Between Benign and Malignant Tumors?

The main difference between these two types of tumor is that benign tumors are usually harmless, whereas malignant tumors cause cancer.

Benign tumors also stay in one area, but malignant tumors can spread throughout the body, affecting different organs and tissues.


Niederhuber, J. E., Brennan, M. F. & Menck, H. R. The National Cancer Data Base report on pancreatic cancer. Cancer 76, 1671–1677 (1995).

Warshaw, A. L. & Fernandez-del Castillo, C. Pancreatic carcinoma. N. Engl. J. Med. 326, 455–465 (1992).

Ahrendt, S. A. & Pitt, H. A. Surgical management of pancreatic cancer. Oncology 16, 725–734 discussion 734, 736–738, 740, 743 (2002).

Kern, S. et al. A white paper: the product of a pancreas cancer think tank. Cancer Res. 61, 4923–4932 (2001).

Anderson, K. E., Potter, J. D. & Mack, T. M. in Cancer Epidemiology and Prevention (eds Schottenfeld, D. & Fraumeni, J. J.) 725–771 (Oxford University Press, New York, 1996).

Lynch, H. T. et al. Familial pancreatic cancer: a review. Semin. Oncol. 23, 251–275 (1996).

Jaffee, E. M., Hruban, R. H., Canto, M. & Kern, S. E. Focus on pancreas cancer. Cancer Cell 2, 25–28 (2002).

Eberle, M. A. et al. A new susceptibility locus for autosomal dominant pancreatic cancer maps to chromosome 4q32-34. Am. J. Hum. Genet. 70, 1044–1048 (2002). Linkage mapping of a new familial pancreatic cancer gene.

Lowenfels, A. B. et al. Hereditary pancreatitis and the risk of pancreatic cancer. International Hereditary Pancreatitis Study Group. J. Natl Cancer Inst. 89, 442–446 (1997).

Whitcomb, D. C. et al. Hereditary pancreatitis is caused by a mutation in the cationic trypsinogen gene. Nature Genet. 14, 141–145 (1996).

Kinzler, K. W. & Vogelstein, B. Lessons from hereditary colorectal cancer. Cell 87, 159–170 (1996).

Cubilla, A. L. & Fitzgerald, P. J. Morphological lesions associated with human primary invasive nonendocrine pancreas cancer. Cancer Res. 36, 2690–2698 (1976). A landmark study providing histological evidence for a ductal cell of origin for pancreatic adenocarcinoma.

Klimstra, D. S. & Longnecker, D. S. K-ras mutations in pancreatic ductal proliferative lesions. Am. J. Pathol. 145, 1547–1550 (1994).

Hruban, R. H. et al. Pancreatic intraepithelial neoplasia: a new nomenclature and classification system for pancreatic duct lesions. Am. J. Surg. Pathol. 25, 579–586 (2001).

Klein, W. M., Hruban, R. H., Klein-Szanto, A. J. & Wilentz, R. E. Direct correlation between proliferative activity and dysplasia in pancreatic intraepithelial neoplasia (PanIN): additional evidence for a recently proposed model of progression. Mod. Pathol. 15, 441–447 (2002).

Moskaluk, C. A., Hruban, R. H. & Kern, S. E. p16 and K-ras gene mutations in the intraductal precursors of human pancreatic adenocarcinoma. Cancer Res. 57, 2140–2143 (1997).

Yamano, M. et al. Genetic progression and divergence in pancreatic carcinoma. Am. J. Pathol. 156, 2123–2133 (2000).

Luttges, J. et al. Allelic loss is often the first hit in the biallelic inactivation of the p53 and DPC4 genes during pancreatic carcinogenesis. Am. J. Pathol. 158, 1677–1683 (2001). References 16–18 document common mutational profiles in PanINs and pancreatic adenocarcinomas occurring in the same patient, providing genetic evidence that PanINs are progenitors of adenocarcinomas.

Wilentz, R. E. et al. Loss of expression of Dpc4 in pancreatic intraepithelial neoplasia: evidence that DPC4 inactivation occurs late in neoplastic progression. Cancer Res. 60, 2002–2006 (2000).

Heinmoller, E. et al. Molecular analysis of microdissected tumors and preneoplastic intraductal lesions in pancreatic carcinoma. Am. J. Pathol. 157, 83–92 (2000).

Rozenblum, E. et al. Tumor-suppressive pathways in pancreatic carcinoma. Cancer Res. 57, 1731–1734 (1997). Mutational profile of a large series of pancreatic adenocarcinomas.

Biankin, A. V. et al. Overexpression of p21(WAF1/CIP1) is an early event in the development of pancreatic intraepithelial neoplasia. Cancer Res. 61, 8830–8837 (2001).

Shields, J. M., Pruitt, K., McFall, A., Shaub, A. & Der, C. J. Understanding Ras: 'it ain't over 'til it's over'. Trends Cell Biol. 10, 147–154 (2000).

Korc, M. et al. Overexpression of the epidermal growth factor receptor in human pancreatic cancer is associated with concomitant increases in the levels of epidermal growth factor and transforming growth factor alpha. J. Clin. Invest. 90, 1352–1360 (1992).

Barton, C. M., Hall, P. A., Hughes, C. M., Gullick, W. J. & Lemoine, N. R. Transforming growth factor alpha and epidermal growth factor in human pancreatic cancer. J. Pathol. 163, 111–116 (1991).

Friess, H. et al. Pancreatic cancer: the potential clinical relevance of alterations in growth factors and their receptors. J. Mol. Med. 74, 35–42 (1996).

Watanabe, M., Nobuta, A., Tanaka, J. & Asaka, M. An effect of K-ras gene mutation on epidermal growth factor receptor signal transduction in PANC-1 pancreatic carcinoma cells. Int. J. Cancer 67, 264–268 (1996).

Sibilia, M. et al. The EGF receptor provides an essential survival signal for SOS-dependent skin tumor development. Cell 102, 211–220 (2000).

Day, J. D. et al. Immunohistochemical evaluation of HER-2/ neu expression in pancreatic adenocarcinoma and pancreatic intraepithelial neoplasms. Hum. Pathol. 27, 119–124 (1996).

Wagner, M. et al. Expression of a truncated EGF receptor is associated with inhibition of pancreatic cancer cell growth and enhanced sensitivity to cisplatinum. Int. J. Cancer 68, 782–787 (1996).

Overholser, J. P., Prewett, M. C., Hooper, A. T., Waksal, H. W. & Hicklin, D. J. Epidermal growth factor receptor blockade by antibody IMC-C225 inhibits growth of a human pancreatic carcinoma xenograft in nude mice. Cancer 89, 74–82 (2000).

Whelan, A. J., Bartsch, D. & Goodfellow, P. J. Brief report: a familial syndrome of pancreatic cancer and melanoma with a mutation in the CDKN2 tumor-suppressor gene. N. Engl. J. Med. 333, 975–977 (1995).

Goldstein, A. M. et al. Increased risk of pancreatic cancer in melanoma-prone kindreds with p16INK4 mutations. N. Engl. J. Med. 333, 970–974 (1995).

Goldstein, A. M., Struewing, J. P., Chidambaram, A., Fraser, M. C. & Tucker, M. A. Genotype-phenotype relationships in U. S. melanoma-prone families with CDKN2A and CDK4 mutations. J. Natl Cancer Inst. 92, 1006–1010 (2000).

Lynch, H. T. et al. Phenotypic variation in eight extended CDKN2A germline mutation familial atypical multiple mole melanoma-pancreatic carcinoma-prone families: the familial atypical mole melanoma-pancreatic carcinoma syndrome. Cancer 94, 84–96 (2002).

Borg, A. et al. High frequency of multiple melanomas and breast and pancreas carcinomas in CDKN2A mutation-positive melanoma families. J. Natl Cancer Inst. 92, 1260–1266 (2000).

Sherr, C. J. The INK4A/ARF network in tumour suppression. Nature Rev. Mol. Cell Biol. 2, 731–737 (2001).

Liu, L. et al. Mutation of the CDKN2A 5′ UTR creates an aberrant initiation codon and predisposes to melanoma. Nature Genet. 21, 128–132 (1999).

Lal, G. et al. Patients with both pancreatic adenocarcinoma and melanoma may harbor germline CDKN2A mutations. Genes Chromosom. Cancer 27, 358–361 (2000).

Krimpenfort, P., Quon, K. C., Mooi, W. J., Loonstra, A. & Berns, A. Loss of p16 Ink4a confers susceptibility to metastatic melanoma in mice. Nature 413, 83–86 (2001).

Sharpless, N. E. et al. Loss of p16 Ink4a with retention of p19Arf predisposes mice to tumorigenesis. Nature 413, 86–91 (2001). References 40 and 41 report the phenotypes of Ink4a-knockout mice.

Zindy, F., Quelle, D. E., Roussel, M. F. & Sherr, C. J. Expression of the p16 INK4a tumor suppressor versus other INK4 family members during mouse development and aging. Oncogene 15, 203–211 (1997).

Nielsen, G. P. et al. Immunohistochemical survey of p16 INK4A expression in normal human adult and infant tissues. Lab. Invest. 79, 1137–1143 (1999).

Sherr, C. J. & DePinho, R. A. Cellular senescence: mitotic clock or culture shock? Cell 102, 407–410 (2000).

Ramirez, R. D. et al. Putative telomere-independent mechanisms of replicative aging reflect inadequate growth conditions. Genes Dev. 15, 398–403 (2001).

Schmitt, C. A. et al. A senescence program controlled by p53 and p16(INK4a) contributes to the outcome of cancer therapy. Cell 109, 335–346 (2002).

Zhu, J., Woods, D., McMahon, M. & Bishop, J. M. Senescence of human fibroblasts induced by oncogenic Raf. Genes Dev. 12, 2997–3007 (1998).

Brookes, S. et al. INK4A-deficient human diploid fibroblasts are resistant to RAS-induced senescence. EMBO J. 21, 2936–2945 (2002).

Serrano, M., Lin, A. W., McCurrach, M. E., Beach, D. & Lowe, S. W. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 88, 593–602 (1997). References 47–49 provide an explanation for the oncogenic cooperation of activated RAS genes and loss of the INK4A /ARF locus.

Luttges, J. et al. The K-ras mutation pattern in pancreatic ductal adenocarcinoma usually is identical to that in associated normal, hyperplastic, and metaplastic ductal epithelium. Cancer 85, 1703–1710 (1999).

Laghi, L. et al. Common occurrence of multiple K-RAS mutations in pancreatic cancers with associated precursor lesions and in biliary cancers. Oncogene 21, 4301–4306 (2002).

Jackson, E. L. et al. Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras. Genes Dev. 15, 3243–3248 (2001).

Chin, L. et al. Cooperative effects of INK4A and RAS in melanoma susceptibility in vivo. Genes Dev. 11, 2822–2834 (1997).

Fisher, G. H. et al. Induction and apoptotic regression of lung adenocarcinomas by regulation of a K-Ras transgene in the presence and absence of tumor suppressor genes. Genes Dev. 15, 3249–3262 (2001).

Sharpless, N. E. & DePinho, R. A. The INK4A/ARF locus and its two gene products. Curr. Opin. Genet. Dev. 9, 22–30 (1999).

Maser, R. S. & DePinho, R. A. Connecting chromosomes, crisis, and cancer. Science 297, 565–569 (2002).

Gorunova, L. et al. Cytogenetic analysis of pancreatic carcinomas: intratumor heterogeneity and nonrandom pattern of chromosome aberrations. Genes Chromosom. Cancer 23, 81–99 (1998).

Artandi, S. E. et al. Telomere dysfunction promotes non-reciprocal translocations and epithelial cancers in mice. Nature 406, 641–645 (2000).

Chin, L. et al. p53 deficiency rescues the adverse effects of telomere loss and cooperates with telomere dysfunction to accelerate carcinogenesis. Cell 97, 527–538 (1999).

Gisselsson, D. et al. Chromosomal breakage-fusion-bridge events cause genetic intratumor heterogeneity. Proc. Natl Acad. Sci. USA 97, 5357–5362 (2000).

Gisselsson, D. et al. Telomere dysfunction triggers extensive DNA fragmentation and evolution of complex chromosome abnormalities in human malignant tumors. Proc. Natl Acad. Sci. USA 98, 12683–12688 (2001). Evidence for a role of telomere attrition in promoting chromosomal instability in the progression of pancreatic adenocarcinoma.

Suehara, N. et al. Telomerase elevation in pancreatic ductal carcinoma compared to nonmalignant pathological states. Clin. Cancer Res. 3, 993–998 (1997).

Venkitaraman, A. R. Cancer susceptibility and the functions of BRCA1 and BRCA2. Cell 108, 171–182 (2002).

Cancer risks in BRCA2 mutation carriers. The Breast Cancer Linkage Consortium. J. Natl Cancer Inst. 91, 1310–1316 (1999).

Goggins, M., Hruban, R. H. & Kern, S. E. BRCA2 is inactivated late in the development of pancreatic intraepithelial neoplasia: evidence and implications. Am. J. Pathol. 156, 1767–1771 (2000).

Sato, N. et al. Correlation between centrosome abnormalities and chromosomal instability in human pancreatic cancer cells. Cancer Genet. Cytogenet. 126, 13–19 (2001).

Aarnio, M., Mecklin, J. P., Aaltonen, L. A., Nystrom-Lahti, M. & Jarvinen, H. J. Life-time risk of different cancers in hereditary non-polyposis colorectal cancer (HNPCC) syndrome. Int. J. Cancer 64, 430–433 (1995).

Goggins, M. et al. Pancreatic adenocarcinomas with DNA replication errors (RER+) are associated with wild-type K-ras and characteristic histopathology. Poor differentiation, a syncytial growth pattern, and pushing borders suggest RER+. Am. J. Pathol. 152, 1501–1507 (1998).

Mahlamaki, E. H. et al. Comparative genomic hybridization reveals frequent gains of 20q, 8q, 11q, 12p, and 17q, and losses of 18q, 9p, and 15q in pancreatic cancer. Genes Chromosom. Cancer 20, 383–391 (1997).

Peltomaki, P. & de la Chapelle, A. Mutations predisposing to hereditary nonpolyposis colorectal cancer. Adv. Cancer Res. 71, 93–119 (1997).

Lynch, H. T., Voorhees, G. J., Lanspa, S. J., McGreevy, P. S. & Lynch, J. F. Pancreatic carcinoma and hereditary nonpolyposis colorectal cancer: a family study. Br. J. Cancer 52, 271–273 (1985).

Yamamoto, H. et al. Genetic and clinical features of human pancreatic ductal adenocarcinomas with widespread microsatellite instability. Cancer Res. 61, 3139–3144 (2001).

Wilentz, R. E. et al. Genetic, immunohistochemical, and clinical features of medullary carcinoma of the pancreas: a newly described and characterized entity. Am. J. Pathol. 156, 1641–1651 (2000).

Hahn, S. A. et al. DPC4, a candidate tumor suppressor gene at human chromosome 18q21.1. Science 271, 350–353 (1996). Identification of SMAD4/DPC4.

Massague, J., Blain, S. W. & Lo, R. S. TGF-β signaling in growth control, cancer, and heritable disorders. Cell 103, 295–309 (2000).

Sirard, C. et al. Targeted disruption in murine cells reveals variable requirement for Smad4 in transforming growth factor beta-related signaling. J. Biol. Chem. 275, 2063–2070 (2000).

Jonson, T. et al. Altered expression of TGF-β receptors and mitogenic effects of TGF-β in pancreatic carcinomas. Int. J. Oncol. 19, 71–81 (2001).

Dai, J. L. et al. Transforming growth factor-beta responsiveness in DPC4/SMAD4-null cancer cells. Mol. Carcinog. 26, 37–43 (1999).

Giehl, K., Seidel, B., Gierschik, P., Adler, G. & Menke, A. TGF-β1 represses proliferation of pancreatic carcinoma cells which correlates with Smad4-independent inhibition of ERK activation. Oncogene 19, 4531–4541 (2000).

Rowland-Goldsmith, M. A., Maruyama, H., Kusama, T., Ralli, S. & Korc, M. Soluble type II transforming growth factor-beta (TGF-beta) receptor inhibits TGF-beta signaling in COLO-357 pancreatic cancer cells in vitro and attenuates tumor formation. Clin. Cancer Res. 7, 2931–2940 (2001).

Hemminki, A. et al. A serine/threonine kinase gene defective in Peutz–Jeghers syndrome. Nature 391, 184–187 (1998).

Solcia, E., Capella, C. & Kloppel, G. Tumors of the Pancreas (ed. Rosai, J.) (Armed Forces Institute for Pathology, Washington DC, 1995).

Pour, P. M. The role of langerhans islets in pancreatic ductal adenocarcinoma. Front Biosci. 2, d271–282 (1997).

Boardman, L. A. et al. Genetic heterogeneity in Peutz–Jeghers syndrome. Hum. Mutat. 16, 23–30 (2000).

Cooper, H. S. in Pathology of the Gastrointestinal Tract (eds Ming, S.-C. & Goldman, H.) 819–853 (Wiliams & Wilkens, Baltimore, 1998).

Olschwang, S. et al. Peutz–Jeghers disease: most, but not all, families are compatible with linkage to 19p13.3. J. Med. Genet. 35, 42–44 (1998).

Olschwang, S., Boisson, C. & Thomas, G. Peutz–Jeghers families unlinked to STK11/LKB1 gene mutations are highly predisposed to primitive biliary adenocarcinoma. J. Med. Genet. 38, 356–360 (2001).

Klimstra, D. S. in Pancreatic Cancer: Advances in Molecular Pathology, Diagnosis and Clinical Management (eds Sarkar, F. S. & Duggan, M. C.) 21–48 (Eaton Publishing, Natick, Massachusetts, 1998).

Jimenez, R. E. et al. Immunohistochemical characterization of pancreatic tumors induced by dimethylbenzanthracene in rats. Am. J. Pathol. 154, 1223–1229 (1999).

Wagner, M. et al. A murine tumor progression model for pancreatic cancer recapitulating the genetic alterations of the human disease. Genes Dev. 15, 286–293 (2001). The first description of a genetically defined mouse model of pancreatic adenocarcinoma.

Yoshida, T. & Hanahan, D. Murine pancreatic ductal adenocarcinoma produced by in vitro transduction of polyoma middle T oncogene into the islets of Langerhans. Am. J. Pathol. 145, 671–684 (1994).

Tosh, D. & Slack, J. M. How cells change their phenotype. Nature Rev. Mol. Cell Biol. 3, 187–194 (2002).

Blau, H. M., Brazelton, T. R. & Weimann, J. M. The evolving concept of a stem cell: entity or function? Cell 105, 829–841 (2001).

Bonner–Weir, S. & Sharma, A. Pancreatic stem cells. J. Pathol. 197, 519–526 (2002).

Elsasser, H.-P., Adler, G. & Kern, H. F. in The Pancreas: Biology, Pathobiology and Disease (Raven Press Ltd, New York, 1993).

Bonner–Weir, S., Stubbs, M., Reitz, P., Taneja, M. & Smith, F. E. in Pancreatic Growth and Regeneration (ed. Sarvetnick, N.) (Karger Landes Systems, Basel, Switzerland, 1997).

Sharma, A. et al. The homeodomain protein IDX-1 increases after an early burst of proliferation during pancreatic regeneration. Diabetes 48, 507–513 (1999).

Vinik, A. I., Pittenger, G. L., Rafaeloff, R., Rosenberg, L. & Duguid, W. in Pancreatic Growth and Regeneration. (ed. Sarvetnick, N.) 183–217 (Karger Landes Systems, Basel, 1997).

Scoggins, C. R. et al. p53-dependent acinar cell apoptosis triggers epithelial proliferation in duct-ligated murine pancreas. Am. J. Physiol. Gastrointest. Liver Physiol. 279, G827–G836 (2000).

Kritzik, M. R. et al. PDX-1 and Msx-2 expression in the regenerating and developing pancreas. J. Endocrinol. 163, 523–530 (1999).

Arnush, M. et al. Growth factors in the regenerating pancreas of γ-interferon transgenic mice. Lab. Invest. 74, 985–990 (1996).

Rooman, I., Heremans, Y., Heimberg, H. & Bouwens, L. Modulation of rat pancreatic acinoductal transdifferentiation and expression of PDX-1 in vitro. Diabetologia 43, 907–914 (2000).

Bachoo, R. M. et al. Epidermal growth factor receptor and Ink4a/Arf. Convergent mechanisms governing terminal differentiation and transformation along the neural stem cell to astrocyte axis. Cancer Cell 1, 269–277 (2002).

Lohr, M. et al. Transforming growth factor-β1 induces desmoplasia in an experimental model of human pancreatic carcinoma. Cancer Res. 61, 550–555 (2001).

Schwarte-Waldhoff, I. et al. Smad4/DPC4-mediated tumor suppression through suppression of angiogenesis. Proc. Natl Acad. Sci. USA 97, 9624–9629 (2000).

Bissell, M. J. & Radisky, D. Putting tumours in context. Nature Rev. Cancer 1, 46–54 (2001).

Olumi, A. F. et al. Carcinoma-associated fibroblasts direct tumor progression of initiated human prostatic epithelium. Cancer Res. 59, 5002–5011 (1999).

Van Dyke, T. & Jacks, T. Cancer modeling in the modern era: progress and challenges. Cell 108, 135–144 (2002).

Ornitz, D. M., Hammer, R. E., Messing, A., Palmiter, R. D. & Brinster, R. L. Pancreatic neoplasia induced by SV40 T-antigen expression in acinar cells of transgenic mice. Science 238, 188–193 (1987).

Glasner, S., Memoli, V. & Longnecker, D. S. Characterization of the ELSV transgenic mouse model of pancreatic carcinoma. Histologic type of large and small tumors. Am. J. Pathol. 140, 1237–1245 (1992).

Quaife, C. J., Pinkert, C. A., Ornitz, D. M., Palmiter, R. D. & Brinster, R. L. Pancreatic neoplasia induced by Ras expression in acinar cells of transgenic mice. Cell 48, 1023–1034 (1987).

Sandgren, E. P., Quaife, C. J., Paulovich, A. G., Palmiter, R. D. & Brinster, R. L. Pancreatic tumor pathogenesis reflects the causative genetic lesion. Proc Natl Acad Sci USA 88, 93–97 (1991).

Sandgren, E. P. et al. Transforming growth factor alpha dramatically enhances oncogene-induced carcinogenesis in transgenic mouse pancreas and liver. Mol. Cell Biol. 13, 320–330 (1993).

Bardeesy, N. et al. Obligate roles for p16(Ink4a) and p19(Arf)-p53 in the suppression of murine pancreatic neoplasia. Mol. Cell Biol. 22, 635–643 (2002).

Sotillo, R. et al. Wide spectrum of tumors in knock-in mice carrying a Cdk4 protein insensitive to INK4 inhibitors. EMBO J. 20, 6637–6647 (2001).

Rane, S. G. et al. Loss of Cdk4 expression causes insulin-deficient diabetes and Cdk4 activation results in β-islet cell hyperplasia. Nature Genet. 22, 44–52 (1999).

Xu, X. et al. Haploid loss of the tumor suppressor Smad4/Dpc4 initiates gastric polyposis and cancer in mice. Oncogene 19, 1868–1874 (2000).

Takaku, K. et al. Gastric and duodenal polyps in Smad4 (Dpc4) knockout mice. Cancer Res. 59, 6113–6117 (1999).

Jishage, K. et al. Role of Lkb1, the causative gene of Peutz–Jegher's syndrome, in embryogenesis and polyposis. Proc. Natl Acad. Sci. USA 99, 8903–8908 (2002).

Miyoshi, H. et al. Gastrointestinal hamartomatous polyposis in Lkb1 heterozygous knockout mice. Cancer Res. 62, 2261–2266 (2002).

Bardeesy, N. et al. Loss of the Lkb1 tumour suppressor provokes intestinal polyposis but resistance to transformation. Nature 419, 162–167 (2002).

Robanus-Maandag, E. et al. p107 is a suppressor of retinoblastoma development in pRb-deficient mice. Genes Dev. 12, 1599–1609 (1998).

Jonkers, J. & Berns, A. Conditional mouse models of sporadic cancer. Nature Rev. Cancer 2, 251–265 (2002).

Gu, G., Dubauskaite, J. & Melton, D. A. Direct evidence for the pancreatic lineage: NGN3+ cells are islet progenitors and are distinct from duct progenitors. Development 129, 2447–2457 (2002).

Chin, L. et al. Essential role for oncogenic Ras in tumour maintenance. Nature 400, 468–472 (1999).

Hennig, R. et al. 5-lipoxygenase and leukotriene b(4) receptor are expressed in human pancreatic cancers but not in pancreatic ducts in normal tissue. Am. J. Pathol. 161, 421–428 (2002).

Maitra, A. et al. Cyclooxygenase 2 expression in pancreatic adenocarcinoma and pancreatic intraepithelial neoplasia: an immunohistochemical analysis with automated cellular imaging. Am. J. Clin. Pathol. 118, 194–201 (2002).

Tucker, O. N. et al. Cyclooxygenase-2 expression is up-regulated in human pancreatic cancer. Cancer Res. 59, 987–990 (1999).

Anderson, K. E., Johnson, T. W., Lazovich, D. & Folsom, A. R. Association between nonsteroidal anti-inflammatory drug use and the incidence of pancreatic cancer. J. Natl Cancer Inst. 94, 1168–1171 (2002).

Oshima, M. & Taketo, M. M. COX selectivity and animal models for colon cancer. Curr. Pharm. Des. 8, 1021–1034 (2002).

Ramaswamy, S. & Golub, T. R. DNA microarrays in clinical oncology. J. Clin. Oncol. 20, 1932–1941 (2002).

Argani, P. et al. Discovery of new markers of cancer through serial analysis of gene expression: prostate stem cell antigen is overexpressed in pancreatic adenocarcinoma. Cancer Res. 61, 4320–4324 (2001).

Iacobuzio-Donahue, C. A. et al. Discovery of novel tumor markers of pancreatic cancer using global gene expression technology. Am. J. Pathol. 160, 1239–1249 (2002).

Rosty, C. et al. Identification of hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein I as a biomarker for pancreatic ductal adenocarcinoma by protein biochip technology. Cancer Res. 62, 1868–1875 (2002).

Han, H. et al. Identification of differentially expressed genes in pancreatic cancer cells using cDNA microarray. Cancer Res. 62, 2890–2896 (2002).

Githens, S. in The Pancreas: Biology, Pathobiology and Disease (eds Liang, V. & Go, W.) 21–55 (Raven Press Ltd, New York, 1993).

Slack, J. M. Developmental biology of the pancreas. Development 121, 1569–1580 (1995).

Kim, S. K. & Hebrok, M. Intercellular signals regulating pancreas development and function. Genes Dev. 15, 111–127 (2001).

Kobitsu, K. et al. Shortened telomere length and increased telomerase activity in hamster pancreatic duct adenocarcinomas and cell lines. Mol. Carcinog. 18, 153–159 (1997).

Edlund, H. Organogenesis: pancreatic organogenesis developmental mechanisms and implications for therapy. Nature Rev. Genet. 3, 524–532 (2002).

Hebrok, M., Kim, S. K. & Melton, D. A. Notochord repression of endodermal Sonic hedgehog permits pancreas development. Genes Dev. 12, 1705–1713 (1998).

Wells, J. M. & Melton, D. A. Vertebrate endoderm development. Annu. Rev. Cell Dev. Biol. 15, 393–410 (1999).

Shen, C. N., Slack, J. M. & Tosh, D. Molecular basis of transdifferentiation of pancreas to liver. Nature Cell Biol. 2, 879–887 (2000).

Harada, T. et al. Interglandular cytogenetic heterogeneity detected by comparative genomic hybridization in pancreatic cancer. Cancer Res 62, 835–839 (2002).

Giardiello, F. M. et al. Very high risk of cancer in familial Peutz–Jeghers syndrome. Gastroenterology 119, 1447–1453 (2000).

Clarke, A. R., Cummings, M. C. & Harrison, D. J. Interaction between murine germline mutations in p53 and APC predisposes to pancreatic neoplasia but not to increased intestinal malignancy. Oncogene 11, 1913–1920 (1995).

Meszoely, I. M., Means, A. L., Scoggins, C. R. & Leach, S. D. Developmental aspects of early pancreatic cancer. Cancer J. 7, 242–250 (2001).

Piecing it together

Scientists are making fascinating discoveries about how brain tumours work, which could move us closer to new and better treatments. But getting there will depend on piecing this information together with our knowledge of the healthy brain.

“Cancer in the brain is a double-edged sword. There’s cancer and then there’s the brain. And the brain has many unique qualities that add to the challenge,” says Walker.

To tackle a puzzle as complex as this, we need to bring scientists together too. Walker thinks it’s vital that cancer scientists work alongside specialists who know how the brain develops and functions.

“There needs to be a meeting of minds, a sharing of the load for us to make real progress,” he says.

And that’s exactly what the Cancer Research UK Brain Tumour Awards are here to do.

Cancer and Post-Transcriptional Control

Modifications, such as the overexpression of miRNAs, in the post-transcriptional control of a gene can result in cancer.

Learning Objectives

Explain how post-transcriptional control can result in cancer

Key Takeaways

Key Points

  • Specific cancers have altered expression of miRNAs changes in the miRNA population of particular cancers varies depending on the type of cancer.
  • Having too many miRNAs can dramatically decrease the RNA population leading to a decrease in protein expression.
  • Studies have found that some miRNAs are specifically expressed only in cancer cells.

Key Terms

  • microRNA: a single-stranded, non-coding form of RNA, having only about 20-30 nucleotides, that has a number of functions including the regulation of gene expression
  • exosome: a vesicle responsible for the selective removal of plasma membrane proteins

Cancer and Post-transcriptional Control

Post-transcriptional regulation is the control of gene expression at the RNA level therefore, between the transcription and the translation of the gene. After being produced, the stability and distribution of the different transcripts is regulated (post-transcriptional regulation) by means of RNA-binding proteins (RBP) that control the various steps and rates of the transcripts: events such as alternative splicing, nuclear degradation (exosome), processing, nuclear export (three alternative pathways), sequestration in DCP2-bodies for storage or degradation, and, ultimately, translation.

Changes in the post-transcriptional control of a gene can result in cancer. Recently, several groups of researchers have shown that specific cancers have altered expression of microRNAs (miRNAs). miRNAs bind to the 3′ UTR or 5′ UTR of RNA molecules to degrade them. Overexpression of these miRNAs could be detrimental to normal cellular activity. An increase in many miRNAs could dramatically decrease the RNA population leading to a decrease in protein expression. Several studies have demonstrated a change in the miRNA population in specific cancer types. It appears that the subset of miRNAs expressed in breast cancer cells is quite different from the subset expressed in lung cancer cells or even from normal breast cells. This suggests that alterations in miRNA activity can contribute to the growth of breast cancer cells. These types of studies also suggest that if some miRNAs are specifically expressed only in cancer cells, they could be potential drug targets. It would, therefore, be conceivable that new drugs that turn off miRNA expression in cancer could be an effective method to treat cancer.

MicroRNA: Overexpression of miRNAs could be detrimental to normal cellular activity because miRNAs bind to the 3′ UTR of RNA molecules to degrade them. Specific types of miRNAs are only found in cancer cells.

Malfunctioning DNA

Tumors grow because of a malfunction in cells' DNA, mainly in genes that regulate cells' ability to control their growth. Some damaged genes may also prevent bad cells from killing themselves to make room for new, healthy cells. "The regulation of cell death so important," Dr. Garcia says. "If your programmed cell death is altered, the cell does not knows when it's time to die and persists. If the cell learns how to block that, and it develops the ability to proliferate, tumors grow more rapidly." Some of these mutations lead to rapid, unchecked growth, producing tumors that may spread quickly and damage nearby organs and tissue. "Malignant cells have the ability to produce enzymes that dissolve the native tissue. This is known as invasiveness," Dr. Garcia says. Other mutations are less aggressive, forming slow-growing tumors that are not cancerous. "Benign tumors don't generally invade," Dr. Garcia says. "They usually push the normal tissue to the side."

Many people carry benign tumors their entire life. Nevi, or moles, are types of benign tumors that may never need treatment. Other types of benign tumors include:

  • Adenomas: These bumps form on the surfaces of G-I tract. "A colon polyp, a classic adenoma, has only a 1 percent chance of becoming cancer in the patient's lifetime," says Jeffrey Weber, MD, Gastroenterologist at our hospital near Phoenix.
  • Fibromas: These tumors of connective tissue may be found in any organ. Fibroid tumors are named for where they form in the body, such as uterine fibroids.
  • Desmoid tumor: These are often more aggressive than most benign tumors and may invade nearby tissue and organs. But they do not metastasize.
  • Hemangiomas: These tumors are a collection of blood vessel cells in the skin or internal organs. They may appear on the skin as a birthmark-like discoloration and often disappear on their own.
  • Lipomas: These soft, round, fatty tumors are often found on the neck or shoulders.
  • Leiomyomas: The most common gynecologic tumors in the United States, these may be found in the uterus. Their growth is fueled by hormones.

Cancer spread in the lymph nodes

Sometimes doctors aren't sure if a cancer has spread to another part of the body or not. So they look for cancer cells in the lymph nodes near the cancer.

Cancer cells in these nodes is a sign that the cancer has started to spread. This is often called having positive lymph nodes. It means that the cells have broken away from the original cancer and got trapped in the lymph nodes. But it isn't always possible to tell if they have gone anywhere else.

New Ideas for Therapy

In fact, research in Dr. Lowe&rsquos lab has already uncovered new aspects of intra-tumor heterogeneity that potentially could inform treatment. For example, many studies of the problem have focused on identifying genetic differences between a person&rsquos tumor cells. But in a recent report in Nature, Dr. Lowe and his co-workers showed that the heterogeneity is not always genetic.

Working in mouse models of T cell acute lymphoblastic leukemia (ALL), an often aggressive type of blood cancer, the researchers found that tumor cells, even genetically identical ones, may behave differently depending on where in the body they are located. This is because the cells&rsquo ability to grow and survive is influenced by the tissue microenvironment &mdash the noncancerous tissues, cells, and molecules that exist close to the tumor.

The findings could have implications for how T cell ALL tumors in different body sites respond to PI3-kinase inhibitors, a new class of drugs entering clinical trials for the disease. &ldquoIt&rsquos conceivable that these drugs might be effective against tumors in some body sites but not others, depending on differences in the local environment,&rdquo Dr. Lowe notes.

The good news, he adds, is that a number of other drugs currently in development work by targeting cells or molecules in a tumor&rsquos surroundings, preventing these factors from supporting tumor growth. Scientists hope it will be possible to eradicate some difficult-to-treat tumors in the future by combining drugs such as PI3-kinase inhibitors, which act on tumor cells, with drugs that work on the tumor microenvironment.

But Dr. Lowe emphasizes that a lot more research is needed. &ldquoThere&rsquos so much we still don&rsquot know about the biology of tumors and their microenvironment,&rdquo he says, &ldquoand we are only beginning to understand the clinical implications of tumor heterogeneity and how to deal with them.&rdquo


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