Identification And Characterization Of Novel Cancer Cell Derived Factors That Dictate Vascular Endothelial Cell Biology

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Cell-cell communication in the tumor microenvironment drives tumor growth and facilitates neovessel recruitment from the adjacent vasculature. The aim of these experiments were to identify novel cancer derived factors that modulate the vascular endothelial response in a paracrine manner. An array of cancer cell lines from multiple tissue types (Panc1; Hep2G; LnCap; Skmel; Hep3B; PL45; SCC25; CaCo2; PaCa2; SKBR3) were grown under normoxic or hypoxic (1% oxygen) conditions for a total of 20 conditions. After 48 hours, conditioned media was collected and filtered prior to testing on endothelial cells. The effects of these media on endothelial apoptosis, proliferation and tube formation were investigated. In tandem with these endothelial cell fate assays, the proteomic and lipidomic profile of these 20 conditions were profiled and assessed using the Berg Interrogative Biology™ platform. 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. Interestingly, 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 the Berg Interrogative Biology™ platform, 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.Specific factors that determine paracrine cell-cell interaction in the tumor microenvironment have been identified and validated using the Berg Interrogative Biology™ platform. Citation Format: Tony Walshe, Justin J. Bourdelais, Arleide Lee, Rakib Ouro-Djobo, Vivek Vishnudas, Michael Kiebish, Rangaprasad Sarangarajan, Niven R. Narain. Identification and characterization of novel cancer cell derived factors that dictate vascular endothelial cell biology. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3463. doi:10.1158/1538-7445.AM2014-3463