Abstract 2320: A multi-domain fusion molecule inhibits tumor growth affecting in-vivo angiogenesis

• Published in: Cancer research (Chicago, Ill.) Ill.), 2012-04, Vol.72 (8_Supplement), p.2320-2320
• Main Authors: Boosani, Chandra Shekhar, Gunda, Venugopal, Verma, Rajkumar, Yakkanti, Sudhakar Akul
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2012-2320

Growth of solid tumors beyond their benign size largely depends on the availability of oxygen and food supply which is accomplished through induced tumor angiogenesis. Inhibition of such de novo angiogenesis should aid in arresting the growth of solid tumors. Besides availability of several monoclonal antibodies and synthetic inhibitors for target molecules that induce tumor angiogenesis, endogenous antiangiogenic molecules are effective candidates with no drug resistance. Several endogenous angioinhibitors have been identified and were proven to inhibit tumor angiogenesis both in-vitro and in-vivo. However, many of them exhibited varied effects in inhibiting tumor growth with multiple mechanism(s) of action. Thus in our present study we developed a fusion antiangiogenic molecule “Combostatin” using the functional domains from two of the known antiangiogenic molecules reported by us. Here we show that Combostatin is an effective inhibitor of angiogenesis and inhibits tumor growth in-vitro and in-vivo. We also show that Combostatin affects several of the antiangiogenic pathways such as endothelial cell proliferation, migration and tube formation which are mediated by its binding to several integrin receptors on the endothelial cell surface. Our studies conclude that Combostatin is a more potent inhibitor of tumor angiogenesis than its parent molecules generated form type IV and Type XVIII collagen. 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 2320. doi:1538-7445.AM2012-2320