Abstract
Abstract Ovarian cancer is the fourth leading cause of cancer-related death among women. The relatively poor prognosis for ovarian cancer (5-year survival of 30-40%) reflects 1) the advanced stage of disease at diagnosis and 2) the frequent development of recurrent disease refractory to front line therapy. Ovarian cancers metastasize by attaching to and invading through the mesothelium, a single cell layer of mesothelial cells lining the peritoneal cavity. The presence of invasive peritoneal metastases is associated with a poor prognosis for ovarian cancer (5 yr survival <25%). We identified the integrin VLA-4 and its ligand VCAM-1 as regulators of mesothelial invasion. VLA-4 expression correlates with the ability of ovarian cancer cells to invade mesothelial monolayers. Additionally, VLA-4 is expressed on primary ovarian cancer cells obtained from patient tumors or ascites. The contribution of VLA-4 to ovarian cancer peritoneal metastasis was evaluated using a mouse xenograft model and function-blocking antibodies directed against VLA-4. Mice were injected intraperitoneally with platinum-resistant human ovarian cancer cells; one week later the mice were randomized into four groups and treated with 1) anti-VLA-4 antibodies, 2) carboplatin, 3) anti-VLA-4 and carboplatin, or 4) control IgG. Treatment with either anti-VLA-4 therapy or carboplatin alone had no effect on tumor burden compared to the IgG control group. However, the combined treatment of anti-VLA-4 and carboplatin significantly reduced tumor burden compared to the control or either treatment alone. This study supports a role for the active involvement of VLA-4 expressed by tumor cells in the regulation of ovarian cancer chemoresponsiveness. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2346.
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