Epithelial ovarian cancer (EOC) will affect 40-50 out of 100,000 women in the U.S. each year. Nearly 75% of these women will present with advanced stages of the disease at the time of diagnosis, when metastasis had already occurred, resulting in a very poor prognosis and a survival rate of <20%. Thus, while early detection is a pressing clinical issue, inhibition of metastatic dissemination will have immediate clinical impact.
Metastases are mainly confined to the peritoneal cavity, indicating that microenvironmental epigenetic factors that modulate intraperitoneal adhesion, motility and invasion play a predominant role in ovarian pathobiology. EOC metastasis occurs via a multi-step process involving alterations in cell adhesion, migration and invasion. In the current accepted model of EOC metastasis, cells from the primary tumor are shed into the peritoneal cavity as single cells or multicellular aggregates (MCA, or spheroids). MCAs are resistant to some forms of chemotherapy and radiation and based on these data we hypothesize that spheroids are more aggressive invading structures than isolated tumor cells. Metastasizing EOC cells encounter a collagen-rich microenvironment, as the submesothelial matrix is comprised primarily of interstitial collagens . Identification of metastasis-promoting genes, the expression of which is under epigenetic control of the ovarian tumor microenvironment, may reveal novel targets for anti-metastatic therapy. We have developed in vitro organotypic models of ovarian cancer growth to mimic cellular events key to intra-peritoneal metastases. Thus, to model primary tumor cells adherent to the ovarian surface, cells are grown on two-dimensional (2D) collagen films. Cells are shed as both single cells and as MCAs that subsequently adhere to and invade 3D submesothelial collagen matrices. These events are modeled in vitro by sub-culturing cells or MCAs onto 3D collagen gels. We will employ these models to identify epigenetic changes in gene expression by cDNA microarray with a final goal of finding markers of metastatic ovarian cancer.
Dr. Maria V. Barbolina joined the faculty of the University of Illinois at Chicago as an Assistant Professor in 2008. She received her M.S. in Biotechnology from the Lomonosov Moscow State Academy for Fine Chemical Technology in 1996 and a PhD in Molecular Biology from the Engelhardt Institute of Molecular Biology Russian Academy of Sciences in 2001. She was a postdoctoral fellow at the State University of New York at Buffalo where under guidance of Dr.Paul Gollnick she studied the mechanisms of RNA-protein binding and regulation of prokaryotic transcription. In 2004 Dr.Barbolina has switched her research interests into the field of cancer research. She began studies of biological mechanisms underlying metastatic progression of ovarian carcinoma in Dr. Sharon Stack’s lab at Northwestern University. In 2006 Dr.Barbolina have joined a lab of Dr. Lonnie Shea at Northwestern University where she added an expertise in tissue engineering to her multidisciplinary research portfolio. She received the Vahlteich scholar award from the UIC College of Pharmacy, three postdoctoral awards from Penny Severns Breast, Cervical and Ovarian Cancer Research Fund, as well as an OCRF Program of Excellence Award. Her current research interests include understanding of the role of chemokine receptors, particularly, fractalkine and lymphotactin, in metastatic ovarian carcinoma.