Growth and Metastasis of Murine Mammary Carcinomas

AvB3 or AvB5 integrins are widely expressed on blood and endothelial cells. Inhibition of the functions of these integrins has been reported to suppress neovascularization and tumor growth, suggesting that they may be critical modulators of angiogenesis. However, mice lacking these integrins exhibit extensive angiogenesis. Tumors arising from s.c. injections of tumor cells into mice lacking one or both integrins show enhanced tumor growth compared with growth in control mice due to both increased angiogenesis and to altered innate immune response. Other data suggest additional roles for these integrins, on either platelets or the tumor cells themselves, in enhancing tumor progression and metastasis. Here, we investigate the involvement of B3 and B5 integrins in the development and progression of mammary carcinomas. We intercrossed mouse mammary tumor virus (MMTV)-c-neu transgenic mice with B3 or B5 or B3B5 integrin-deficient mice and observed that multiple, large mammary tumors developed in 100% of mice on all genetic backgrounds. A statistically significant earlier onset of tumor growth was observed in the MMTV-c-neu/B3B5 integrin-null females compared with control mice. No major differences were observed in tumor size or number, vessel number or vessel structure and lung metastases were observed with similar frequency and size in all strains. MMTV-c-neu/B3B5 integrinnull mice had higher numbers of mammary acini, which may account for the earlier onset of tumors in this strain. These data indicate that AvB3 or AvB5 integrins are not essential for tumor growth and progression, although they might play some role in mammary gland development. (Cancer Res 2005; 65(22): 10324-9)