Metastasis Suppressors

Cancer treatment has principally focused on destroying the primary tumor or at least in arresting its growth. Although vast improvements in methods of surgery, radiation and chemotherapy have taken place, all too often there have not been corresponding improvements in patient survival. Treatment methods that focus on the primary cancer typically fail after the cancer has metastasized.

I described the metastatic process in my article, Understanding and Controlling Metastasis. It is apparent that tumor cells must acquire altered cellular properties in order to metastasize. They must loosen their adhesiveness to other cells to begin their migration through tissues. They must secrete enzymes that digest the extracellular matrix lining the cells, connective tissue, and the endothelial lining of blood vessels to provide a pathway for their migration. After transport to other tissues or organs, the cancer cells must respond to different signals for attachment to the blood vessels, migration through the vessel wall, and finally colonization and growth in the new tissue or organ.

The role of metastasis suppressors

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. 2Eight metastasis suppressors have been identified, and most act by altering aspects of signal transduction. 3 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.

Go To Page: 1 2