Examining the Role of Cancer-Associated Mesothelial Cells in Ovarian Cancer Metastasis

Project summary

Ovarian cancer is the most lethal gynecological malignancy. As with other solid tumors, the majority of deaths are attributable to development of metastatic disease. Despite efforts to identify effective treatment regimens, better understanding the drivers of ovarian cancer metastasis remains critical to improve patient outcomes.

Metastasis is a complex process involving interactions between cancer cells and surrounding cell types at the metastatic site, termed the tumor microenvironment (TME). The TME influences the ability of a tumor cell to form a metastatic implant. Ovarian cancer is unique in that rather than spreading via the bloodstream (as most solid tumors do) cells are shed from the primary tumor into the abdominal cavity to form metastatic implants on organs such as the omentum, bowel mesentery, and other sites.

The ovarian cancer TME includes a single cell layer of mesothelial cells lining these organs. Adhesion of ovarian tumor cells to this mesothelial cell layer is a key early event in metastatic seeding. Ovarian tumor cells must then compromise this cell layer to access the underlying matrix and invade it to form successful metastatic implants. Little is understood about this process. In this work, we will answer the question: do the mesothelial cells serve as facilitators to the development of ovarian cancer metastasis? Understanding these pathways would allow for identification of points of therapeutic intervention to block the spread of this deadly disease.

This grant was made possible in part by a generous donation from Ovarian Cycle Orlando in memory of Kelly, Carol M., Carol T., Adi, Rose, Judi, Vicky, Terry, Wendy, Adriana, Sherry P., and all of their Teal Angels.