Metastasis of epithelial ovarian carcinoma is currently incurable. One way to change this situation is to develop new approaches and drugs that either alone or in combination with already existing ones are capable of fighting metastatic disease. Our previously published studies indicated that a protein located on the cell surface called fractalkine receptor is expressed in the majority of cases of epithelial ovarian carcinoma. Further these studies suggested that fractalkine receptor could help formation and growth of metastasis when stimulated with another protein, its ligand. This protein belongs to a large class of proteins that has been extensively and successfully targeted by drugs. Our preliminary data demonstrate that if we decrease expression of fractalkine receptor it leads to significant slowing of metastatic growth in an animal model. Motivation for further studies stems from the premise that fractalkine could be a novel potential drug target against epithelial ovarian carcinoma metastasis.
In Aim 1 we will either reduce or increase the expression of fractalkine receptor in mouse ovarian carcinoma cells and inject these cells into mouse abdomens to mimic peritoneal dissemination of malignant cells throughout the peritoneal cavity. We will observe mice until their health status will decline and demand sacrifice. The goal of these experiments is to establish a correlation between expression of fractalkine receptor and survival. These results will inform whether reduction of fractalkine receptor expression is necessary to retard metastatic spread to render the disease “chronic” rather than a deadly one.
In Aim 2 we will determine the impact of the ligand for the fractalkine receptor on formation of metastasis at several commonly colonized organs, such as omentum, peritoneal wall, and others. We will determine the effect of blocking this ligand on development of omental metastasis. These results will inform regarding the effect of microenvironment existing in the peritoneal cavity on the possibility of development metastasis in the future when malignant cells arrive at the scene.
These studies will ultimately lead to validation of the fractalkine receptor and its ligand as potential new drug targets against metastatic epithelial ovarian carcinoma. Because fractalkine receptor is expressed in the majority of primary and metastatic epithelial ovarian carcinoma, we think that targeting the fractalkine network could provide relief from expanding metastasis in the majority of the patients.
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.