Abstract 1356: Vascular endothelial growth inhibitor - potential role in targeted therapy in kidney neoplasma via angiogenic inhibition

Abstract

Abstract Vascular endothelial growth inhibitor (VEGI, also known as TNFSF15) is an anti-angiogenic cytokine found to be associated with tumour-related vasculature in certain maligancies. Three isoforms, VEGI 251, VEGI192, and VEGI174, have been identified, all sharing a common extracellular domain of 151 C-terminal amino acid sequence critical for biological activity of all three isoforms. Previous studies showed tumor inhibitory effect of truncated recombinant VEGI proteins in breast and colorectal cancer xenograft models, however, the antitumor activity of the full length VEGI molecules have not been well characterized in other malignancies, including kidney neoplasm. The objective of the present study was set to evaluate biological impact of forced expression of full length VEGI-174 in a renal cell carcinoma (RCC) cell line, 786-O, and in 786-O derived xenograft models. We found that Increased VEGI-174 expression in 786-O cells did not affect cell growth and apoptosis in vitro, but did reduce cell adhesion and the ability of endothelial cells to form capillary-like structures in co-culture. Subcutaneous xenograft models were successfully established using the 786-O RCC cells with or without forced expression of VEGI-174. Significantly reduced tumor volume, accompanied by reduced tumor microvessel density and decreased Ki67 and VEGFR2 expression, was observed in animals injected with VEGI-174 transfected 786-O cells compared to those in the control groups. Our results demonstrated that increased expression of full length VEGI-174 in RCC 786-O cells resulted in significant reduction in tumor volume most likely via angiogenic inhibition rather than on tumor growth per se. Despite the lack of antitumor effect of full length VEGI174 in some xenograft tumor models in other studies, our results suggest that antitumor effect of the full length VEGI-174 may be cancer type specific, and VEGI-174 may still be a valuable candidate toward angiogenesis based cancer therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1356. doi:1538-7445.AM2012-1356