Metastasis suppressor

A metastasis suppressor is a protein that acts to slow or prevent metastases (secondary tumors) from spreading in the body of an organism with cancer. Metastasis is one of the most lethal attributes of cancer. This attribute is responsible for about ninety percent of human cancer deaths (Olle, David. "Metastasis Suppressors." Suite 101. Web. 05 Oct. 2009.). These proteins that act to slow or prevent metastases are different from ones that act to suppress tumor growth. Genes for about a dozen such proteins are known in humans and other animals (Sobel, ME. 1990. Metastasis suppressor genes. Journal of the National Cancer Institute 82: 267-276.).

The treatment of cancer has usually been aimed at destroying the primary tumor or at least in stopping its growth. Even though, major improvements in the methods of surgery, radiation and chemotherapy have taken place, all often enough there have not been corresponding improvements in patient survival. Treatment methods that focus on the primary cancer typically fall short in aiding the patient after the cancer has metastasized (Olle, David. "Metastasis Suppressors." Suite 101. Web. 05 Oct. 2009.).

Metastasis suppressors act by different mechanisms than tumor suppressors, and have no effect on primary tumors. Tumor suppressors, however, also block metastasis, since metastasis is dependent tumorigenicity (Suite 101. Web. 05 Oct. 2009.). Eight metastasis suppressors have been identified, and most act by altering aspects of signal transduction. NM23 is a suppressor active in melanoma, breast and colon cancers, and apparently inhibits the functioning of a kinase enzyme that promotes cell division. MKK4 is a suppressor active in prostate and ovarian cancers, and apparently functions by facilitating apoptosis, or death of abnormal cells such as cancer cells. KAI1 is found in prostate and breast cancers, and forms complexes with proteins called integrins. Integrins are one of the structures that link cells together, and the complex formation may inhibit detachment and migration of the cancer cells. BRMS1 promotes the activity of the gap junctions of cells. The gap junctions are found on the cell membranes and allow for chemical and electrical communication between cells. It has been proposed that this communication between metastic tumor cells might contribute to inhibition of metastic growth. KISS1 is found in melanoma and breast cancers, and acts by synthesizing a protein receptor. RHOGD12 is active in bladder cancer, and inhibits proteins that aid in cancer cell migration. CRSP3 and VDUP1 are both active in melanoma. CRSP3 is a co-activator of genes involved in cancer growth, while VDUP1 inhibits a protein involved in cell proliferation (Olle, David. "Metastasis Suppressors.").

Metastasis suppressor genes may offer valuable mechanistic insight for guiding specific therapeutic strategies, which may include drug induced reactivation of metastasis suppressor genes and their signaling pathways. Clinical assessment of metastasis suppressor gene product status in disseminated cancer cells may improve the accuracy of predicting the prognosis in patients with clinically localized disease ("Metastasis suppression: the evolving role of metastasis suppressor genes for regulating cancer cell growth at the secondary site." NCBI, Mar. 2003.). Before any new treatments are implemented for general use, doctors conduct studies to find out whether the treatment is both safe for patients and effective against the disease. The results of such studies will ultimately provide the answers needed to continue work on antimetastasis drug development. Future studies should however, focus on treatment at the secondary tumor sites. This is how we will make progress in fighting this disease.^[1] These proteins are different from ones that act to suppress tumor growth.^[2] Genes for about a dozen such proteins are known in humans and other animals, including BRMS1, CRSP3, DRG1, KAI1, KISS1, NM23, and various TIMPs.^[3][4]

References

1. ^ Sobel, ME. 1990. Metastasis suppressor genes. Journal of the National Cancer Institute 82: 267-276.
2. ^ Yoshida, BA, Sokoloff, MM, Welch, DR, Rinker-Schaeffer CW. 2000. Metastasis-suppressor genes: a review and perspective on an emerging field. Journal of the National Cancer Institute 92: 1717-1730.
3. ^ Shevde, LA, Welch, DR. 2003. Metastasis suppressor pathways - an evolving paradigm. Cancer Letters, 198: 1-20.
4. ^ Jackson (Ed.), Paul (2007). New Developments in Metastasis Suppressor Research. Nova Science Pub Inc. ISBN 160021603X. 

"The Basics of Cancer." Amyshah.com Biomedical Engineering blog. Web. 21 Nov. 2009. <http://www.amyshah.com/cancer/the-basics-of-cancer/>. Kauffman, EC, VL Robinson, WM Stadler, MH Sokoloff, and CW Rinker-Schaeffer. "Metastasis suppression: the evolving role of metastasis suppressor genes for regulating cancer cell growth at the secondary site." NCBI, Mar. 2003. Web. 21 Nov. 2009. <http://www.ncbi.nlm.nih.gov/pubmed/12576866>. "Nature Reviews Cancer." Nature Review. Nature publishing group, 11 Nov. 2009. Web. 05 Oct. 2009. <http://www.nature.com/nrc/index.html>. Olle, David. "Metastasis Suppressors." Web. 05 Oct. 2009. Pecorino, Lauren. Molecular Biology of Cancer. 2nd ed. New York: Oxford UP, 2005. Print. Shevde, LA, Welch, DR. 2003. Metastasis suppressor pathways - an evolving paradigm. Cancer Letters, 198: 1-20 Sobel, ME. 1990. Metastasis suppressor genes. Journal of the National Cancer Institute 82: 267-276. "Understanding Cancer Series: Cancer." National Cancer Institute. U.S. National Institutes of health. Web. 21 Nov. 2009. <http://www.cancer.gov/cancertopics/understandingcancer/cancer/Slide8>. WordNet Search 3.0. Web. 19 Nov. 2009. <http://wordnetweb.princeton.edu/perl/webwn?s=metastasis>. Yoshida, BA, Sokoloff, MM, Welch, DR, Rinker-Schaeffer CW. 2000. Metastasis-suppressor genes: a review and perspective on an emerging field. Journal of the National Cancer Institute 92: 1717-1730.