P.10

Sunday, May 27

P.

P.10

Background: The tumor environment has been shown to contribute to tumor growth as stromal cells undergo gene expression changes that stimulate cancer cell growth. Ovarian cancer (OC) ascites constitute a unique tumor environment. Soluble factors in ascites create a protective environment by activating survival pathways in tumor cells to inhibit drug-induced apoptosis. However, little is known about gene expression in mesothelial cells in response to the surrounding ascites. We conducted a comparative analyis of global gene expression changes in mesothelial cells after OC ascites treatment and compare this to treatment with benign peritoneal fluids.

Methods: We generated gene expression profiles of mesothelial cells isolated from the peritoneal lavage of a patient with a benign conditon and treated with serous OC ascites or benign peritoneal fluids. Differential gene expression and gene ontology analyses were performed.

Results: Mesothelial cells undergo extensive gene expression changes in response after treatment with OC ascites. Upregulated genes in response to OC ascites include constituents of cell cycle, cell death, cell assembly and organization, cell growth and proliferation and cell-to-cell signaling and interactions among others. Genes implicated in cellular movement and development, DNA replication and nucleic acid metabolism were supressed after OC ascites treatment. OC ascites treatment triggered alterations in pathway expression linked to Akt, NF-kB, HNF-4 and vascular endothelial growth factor (VEGF).