This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services 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 Furger, K. A. Articles by Tuck, A. B. Search for Related Content PubMed PubMed Citation Articles by Furger, K. A. Articles by Tuck, A. B.

---

Angiogenesis, Metastasis, and the Cellular Microenvironment

ß₃ Integrin Expression Increases Breast Carcinoma Cell Responsiveness to the Malignancy-Enhancing Effects of Osteopontin¹

¹ London Regional Cancer Centre; Departments of ² Oncology and ³ Pathology, University of Western Ontario; and ⁴ Department of Pathology, London Health Sciences Centre, London, Ontario, Canada

Requests for reprints: Alan B. Tuck, Department of Pathology, London Health Sciences Centre, University Campus, P. O. Box 5339, STN B, London, Ontario, Canada N6A 5A5. Phone: (519) 685-8500 x 36361 or (519) 685-8651; Fax: (519) 663-2930. E-mail: atuck{at}uwo.ca

Osteopontin (OPN) is a secreted phosphoprotein that has been associated with malignancy of breast and other cancers. OPN binds to several cell surface integrins including _vß₃, _vß₅, and _vß₁. Although the relative contribution of these integrins to breast cancer cell malignancy is uncertain, correlative studies suggest that _vß₃ may be particularly associated with increased tumor aggressiveness. Previously, we reported that tumorigenic, nonmetastatic 21NT mammary carcinoma cells respond to OPN through _vß₅ and _vß₁ but not _vß₃. Here, we determined that 21NT cells lack ß₃ expression, and we asked whether expression of _vß₃ could enhance the ability of breast cancer cells to respond to the malignancy-promoting effects of OPN both in vitro and in vivo. 21NT cells stably transfected with ß₃ showed significantly increased adhesion, migration, and invasion to OPN in vitro compared with vector control. To determine if ß₃ could also enhance the response of breast epithelial cells to OPN in vivo, cells stably transfected with both ß₃ and OPN (NT/Oß₃) were injected into the mammary fat pad of female nude mice and primary tumor growth was assessed relative to controls. Mice injected with NT/Oß₃ cells demonstrated a significantly increased primary tumor take (75% of mice) compared with controls (0–12.5% of mice) as well as a decreased tumor doubling time and a decreased tumor latency period. These results suggest that increased expression of the _vß₃ integrin during breast cancer progression can make tumor cells more responsive to malignancy-promoting ligands such as OPN and result in increased tumor cell aggressiveness.

Key Words: breast cancer • osteopontin • ß₃ integrin • malignant cell behavior • tumorigenicity

This article has been cited by other articles:

				A. L. Allan, R. George, S. A. Vantyghem, M. W. Lee, N. C. Hodgson, C. J. Engel, R. L. Holliday, D. P. Girvan, L. A. Scott, C. O. Postenka, et al. Role of the Integrin-Binding Protein Osteopontin in Lymphatic Metastasis of Breast Cancer Am. J. Pathol., July 1, 2006; 169(1): 233 - 246. [Abstract] [Full Text] [PDF]

				S. De, O. Razorenova, N. P. McCabe, T. O'Toole, J. Qin, and T. V. Byzova VEGF-integrin interplay controls tumor growth and vascularization PNAS, May 24, 2005; 102(21): 7589 - 7594. [Abstract] [Full Text] [PDF]