Abstract 2278: Tumor microenvironment might be more important than pro-angiogenic chemotactic factors for tumor angiogenesis

Abstract

During angiogenesis, many different tumor cytokines have been known to be involved in the regulation of chemotactic endothelial cell migration. Among those, a vascular endothelial growth factor (VEGF) is one of the most essential pro-angiogenic factors and the blockage of VEGF action through competitive inhibition on its receptor or by using of neutralizing antibody such as avastin has been considered as a promising anti-cancer approach to treat several solid tumors. However, despite their ability of releasing VEGF, some cancers show scarce angiogenesis and resistance to avastin treatment. To explore key factors deciding tumor angiogenesis apart from well-known pro-angiogenic cytokines, we compared the pro-angiogenic capability of the AMC-HN9 head and neck cancer cell line (HN9) which has a low degree of angiogenesis in vivo and are reluctant to avastin treatment with that of the highly angiogenic AMC-HN3 cancer cell line (HN3). Of interest, in vitro cytokine assay of HN9 culture media revealed no difference in the secretion profile of pro-angiogenic cytokines such as VEGF, PlGF, FGF2 and PDGF compared with those of HN3. In addition, HN9 media could strongly promoted tubular formation of HUVECs and migration of fibroblasts in vitro as much as HN3 could. Next, we proceeded to HN9 xenograft co-injected with ECM molecules including fibronectin, collagen III or matrigel. In the co-injected xenografts, density of CD34 positivity significantly increased and the tumor growth exceeded that of HN9 alone-injected ones. Moreover, prominent fibroblast infiltration adjacent to tumor vessels was detected in the co-injected xenografts. Taken together, these results imply that the formation of extracellular matrix surrounding tumor cells and the presence of activated fibroblasts are pre-requisites and more decisive in angiogenesis than tumor secreted pro-angiogenic cytokine per se. 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 2278.