Abstract 2321: Expression of functional forms of αvβ3 and αvβ5 integrins, laminin-5 and vitronectin in common human tumors: Consequences for cilengitide targeting

Abstract

Abstract Interactions between integrins and the extracellular matrix are believed to play an important role in tumor cell survival, division and metastasis, and in tumor angiogenesis. We studied the expression of integrins αvβ3 and αvβ5, and their key ligands in the extracellular matrix in freshly frozen sections of human colorectal, breast, lung and ovarian tumors. We applied immunohistochemistry using anti-integrin monoclonal antibodies specific for functional heterodimeric forms. Prominent expression of αvβ3 was strongly associated with tumor-related vessels (20/21 colorectal, 31/33 lung, 19/19 breast and 7/10 ovarian) but also in other stromal (fibroblastic) cells in >80% of the cases. αvβ5 was almost uniformly detectable in tumor stroma including vessels, showing a considerable expression in tumor cells also (mostly in lung and breast cancers). The expression of activated vitronectin in the stroma was less abundant (3/21 colorectal, 22/33 lung, 13/19 breast and 3/10 ovarian). Laminin-5 was mainly located close to tumor cells in basal lamina-like pattern and showed a considerable expression in colorectal, lung and ovarian but not in breast cancers. We conclude that targeting of αvβ3 by cilengitide may exert potent anti-stroma effects as well. The largely varying spatial distributions and expression of integrins and their ligands should be considered in targeting strategies. Frequency (%) of moderate or strong expression (i.e. in at least 10% of tumor cells) of antigens of interest in human tumors. ColorectalLungBreastOvarya) αvβ3Tumour cells0151620 Stromal cells90685870 Vessels959110070b) αvβ5Tumour cells29587440 Stromal cells9010010070c) VitronectinTumour cells24502140 Stromal cells15656833d) Laminin-5Tumour cells553030 Stromal cells100a / 0b97a / 73b21a / 40b80a / 25baClose to tumor cells; bdistant from tumor cells. 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 2321.