Abstract A22: Identification of novel tumor derived factors that inhibit angiogenesis

Background: Cell-cell communication in the tumor micro-environment drive tumor growth and facilitate neovessel recruitment from the adjacent vasculature. The present study was designed to identify novel cancer derived factors that modulate the vascular endothelial response in a paracrine manner. Methods: An array of cancer cell lines from multiple tissue types (Panc1; HepG2; LnCap; Skmel; Hep3B; PL45; SCC25; CaCo2; PaCa2; SKBR3) were grown under normoxic or hypoxic (1% oxygen) conditions for a total of 20 different conditions. After 48 hours, conditioned media was collected and filtered prior to testing on endothelial cells. The effects of the conditioned media on endothelial apoptosis, proliferation and tube formation were investigated. In tandem with these endothelial cell fate assays, the proteomic profile of these 20 conditions was profiled and assessed using the Berg Interrogative Biology™ platform. Results & Discussion: Our results reveal that conditioned media from all cancer cells tested can alter endothelial cell apoptosis, proliferation rate and tube formation in 3D matrigel assays i.e. critical cell fate decisions that enable formation of nascent vessel formation. As predicted, the predominant effect of tumor-derived conditioned media on endothelial apoptosis was a protective anti-apoptotic effect, with the discernable exception of normoxic Panc1 derived media. An unexpected finding was the general anti-proliferative effects of tumor-derived conditioned media on endothelial cell growth, with the exception of Hep2G, LnCap and PaCa2 cell derived media. Using a media fractionation strategy and Interrogative Biology™, we identified several endothelial anti-apoptotic candidates from Panc1 cells within a unique molecular weight range. Upon application of ASO gene knockdown in Panc1 cells, these targets were verified for apoptotic and proliferation effects on vascular endothelial cells. Conclusion: Specific factors that determine paracrine cell-cell interaction in the tumor microenvironment have been identified and validated employing Berg Interrogative Biology™. The technology presented herein represents a viable platform for identifying clinically relevant biomarkers and factors that alter cancer angiogenesis. Citation Format: Tony E. Walshe, Justin Bourdelais, Arleide Lee, Rakibou Ouro-Djobo, Vivek Vishnudas, Rangaprasad Sarangarajan, Niven Narain. Identification of novel tumor derived factors that inhibit angiogenesis. [abstract]. In: Proceedings of the AACR Special Conference: Tumor Angiogenesis and Vascular Normalization: Bench to Bedside to Biomarkers; Mar 5-8, 2015; Orlando, FL. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(12 Suppl):Abstract nr A22.