MARION C. COHEN
Barnard College, 1960
My laboratory has had a long standing interest in how cytokines modify the behavior of tumor cells with a particular focus on metastasis. It is generally accepted that tumor cells attach to vascular endothelial cells during their transport in the circulation which allows them to implant and invade at distant sites. We and others have found that exposure of endothelial cells to inflammatory cytokines such as TNF- a or IL-1 leads to increased expression of adhesion molecules to which these circulating tumor cells can attach. Infiltrating tumor macrophages are commonly thought to be the source of the cytokines. However, we have considered the possibility that it is the tumor cells themselves that release the cytokines locally. Using a human model of breast cancer we have found that tumor cells can release TNF- a , a cytokine with many different activities including the ability to regulate the expression of adhesion molecules on endothelial cells. Our system includes cell lines that have different invasive and metastatic characteristics and the cytokine that we first studied was TNF- a . We found that TNF- a message expression increases in metastatic cell lines as compared to non-metastatic cells. TNF- a secretion upon PMA stimulation also positively correlates with metastatic ability. Other experiments showed that conditioned media from breast cancer cells is chemotactic for these cells and can also upregulate expression of VCAM-1 by endothelial cells. Anti-TNF- a antibodies could partially abrogate both of these activities. Breast cancer cells were also able to secrete other cytokines such as MCP-1 and IL-8. We are currently trying to determine the relative role these various cytokines have with respect to tumor cell metastasis.
Cohen, M.C., and Cohen S. Cytokine function: a study in biologic diversity. Am. J. Clin. Path., 105:589, 1996.
Cohen, M.C., Bereta M. and Bereta, J. Effect of cytoline on tumor cell-endothelial interactions.
Indian J. Biochem. Biophys., 34:199, 1997.
Castro, T.A., and Cohen, M.C. Cytokine production by breast cancer cells (Abstract) Experimental Biology, 2002
Fernandes, H., Koneru, B., Fernandes, N., Hameed, M., Cohen, M.C., Raveche, E., and Cohen S.
Investigation of promoter polymorphisims in the TNF- a and IL-10 genes in liver transplant patients. Transplantation, 73:1886, 2002.