This Article Full Text Full Text (PDF) Supplementary Data Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Taverna, D. Articles by Hynes, R. O. Search for Related Content PubMed PubMed Citation Articles by Taverna, D. Articles by Hynes, R. O.

A Direct Test of Potential Roles for ß3 and ß5 Integrins in Growth and Metastasis of Murine Mammary Carcinomas

¹ Howard Hughes Medical Institute, Center for Cancer Research, Massachusetts Institute of Technology, Cambridge; ² Department of Biomedical Sciences, Tufts University School of Veterinary Medicine, North Grafton, Massachusetts; and ³ Unit of Gynecological Oncology, Institute for Cancer Research and Treatment, Department of Oncological Sciences, University of Torino, Candiolo (To), Italy

Requests for reprints: Richard O. Hynes, Howard Hughes Medical Institute, Center for Cancer Research, Massachusetts Institute of Technology, 40 Ames Street, E17-227, Cambridge, MA 02139. Phone: 617-253-6422; Fax: 617-253-8357; E-mail: rohynes{at}mit.edu.

vß3 or vß5 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 ß3 and ß5 integrins in the development and progression of mammary carcinomas. We intercrossed mouse mammary tumor virus (MMTV)-c-neu transgenic mice with ß3 or ß5 or ß3ß5 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/ß3ß5 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/ß3ß5 integrin-null mice had higher numbers of mammary acini, which may account for the earlier onset of tumors in this strain. These data indicate that vß3 or vß5 integrins are not essential for tumor growth and progression, although they might play some role in mammary gland development.

This article has been cited by other articles:

				I. Burvenich, S. Schoonooghe, L. Vervoort, C. Dumolyn, E. Coene, L. Vanwalleghem, J. Van Huysse, M. Praet, C. Cuvelier, N. Mertens, et al. Monoclonal antibody 14C5 targets integrin {alpha}v{beta}5 Mol. Cancer Ther., December 1, 2008; 7(12): 3771 - 3779. [Abstract] [Full Text] [PDF]

				Y. Monnier, P. Farmer, G. Bieler, N. Imaizumi, T. Sengstag, G. C. Alghisi, J.-C. Stehle, L. Ciarloni, S. Andrejevic-Blant, R. Moeckli, et al. CYR61 and {alpha}V{beta}5 Integrin Cooperate to Promote Invasion and Metastasis of Tumors Growing in Preirradiated Stroma Cancer Res., September 15, 2008; 68(18): 7323 - 7331. [Abstract] [Full Text] [PDF]

				S. Huveneers, I. van den Bout, P. Sonneveld, A. Sancho, A. Sonnenberg, and E. H.J. Danen Integrin {alpha}v{beta}3 Controls Activity and Oncogenic Potential of Primed c-Src Cancer Res., March 15, 2007; 67(6): 2693 - 2700. [Abstract] [Full Text] [PDF]

				S. Maubant, D. Saint-Dizier, M. Boutillon, F. Perron-Sierra, P. J. Casara, J. A. Hickman, G. C. Tucker, and E. Van Obberghen-Schilling Blockade of {alpha}vbeta3 and {alpha}vbeta5 integrins by RGD mimetics induces anoikis and not integrin-mediated death in human endothelial cells Blood, November 1, 2006; 108(9): 3035 - 3044. [Abstract] [Full Text] [PDF]