The dissemination of ovarian cancer cells throughout the abdominal cavity is reponsible for mortality in ovarian cancer patients. Therefore, studies addressing the regulation of genes that contribute to the invasion and metastases of ovarian cancer cells may lead to new therapies. One of the genes involved in tumor development is c-Met, a tyrosine kinase receptor for hepatocyte growth factor (HGF). Receptor tyrosine kinases (RTK) are signaling molecules that signal inside the cell and ultimately activate gene expression.
Our preliminary data show that c-Met is overexpressed in ovarian cancer and that it regulates proteins (proteases) that are important in the disolution of tissue around tumor cells. Other studies have shown that c-Met can regulate the growth and aggressiveness of breast cancer cells, but our knowledge of c-Met function in ovarian cancer is limited.
We plan to determine the expression and activation pattern of c-Met in ovarian cancer using a tissue micro array (a method to assemble different tissues from ovarian cancer patients in one 1×1 inch paraffin block). C-Met expression will be correlated with traditional prognostic factors such as disease outcome, tumor size and extension. Since cancer cells are often surrounded by normal cells from the stroma we will use a co-culture model to determine if c-Met is involved in the interaction of ovarian cancer cells with other cells of the peritoneum (e.g. fibroblasts, mesothelial cells). Finally, we will inhibit c-Met and investigate whether its inhibition reduces the growth and dissemination of ovarian cancer cells. In summary, these studies will test the hypothesis that c-Met is a therapeutic target for patients with ovarian cancer.
Chair and Professor, Department of Obstetrics and Gynecology University of Chicago Ernst Lengyel, M.D., Ph.D., a Gynecologic Oncologist, is Chair and a Professor in the Department of Obstetrics and Gynecology at the University of Chicago. He graduated magna cum laude from the University of Munich in 1992 with a doctorate in medicine, followed by a research fellowship at MD Anderson Cancer Center. He completed his residency at the University of Munich and then entered the combined Gynecologic Oncology fellowship program at the University of California/San Francisco (UCSF) and Stanford. In 2004, after one year on the clinical faculty at UCSF, he joined the University of Chicago faculty as a research scientist and clinician. In 2008 he was awarded the Burroughs Wellcome Fund Clinical Scientist Award in Translational Research.
Dr Lengyel directs a translational research laboratory focused on understanding ovarian cancer metastasis and on developing and testing new treatments for ovarian cancer. Specifically, he looks at interactions of ovarian cancer cells with the normal cells surrounding them to understand how the cellular microenvironment affects the growth of cancer cells. The major goal of his laboratory is to translate his research findings into novel therapeutic treatments that will improve the survival of those with this devastating disease. His primary clinical focus is the surgical treatment of patients with ovarian cancer.
For more information on Dr. Lengyel’s research and clinical practice at the University of Chicago see: