This Article Full Text Full Text (PDF) Supplementary Data 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 Xue, C. Articles by Segall, J. E. Search for Related Content PubMed PubMed Citation Articles by Xue, C. Articles by Segall, J. E.

ErbB3-Dependent Motility and Intravasation in Breast Cancer Metastasis

Departments of ¹ Anatomy and Structural Biology, ² Molecular Pharmacology, ³ Pathology, and ⁴ Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York

Requests for reprints: Jeffrey E. Segall, Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10801. Phone: 718-430-4237; Fax: 718-430-8996; E-mail: segall{at}aecom.yu.edu.

A better understanding of how epidermal growth factor receptor family members (ErbBs) contribute to metastasis is important for evaluating ErbB-directed therapies. Activation of ErbB3/ErbB2 heterodimers can affect both proliferation and motility. We find that increasing ErbB3-dependent signaling in orthotopic injection models of breast cancer can enhance intravasation and lung metastasis with no effect on primary tumor growth or microvessel density. Enhanced metastatic ability due to increased expression of ErbB2 or ErbB3 correlated with stronger chemotaxis and invasion responses to heregulin ß1. Suppression of ErbB3 expression reduced both intravasation and metastasis. A human breast cancer tumor tissue microarray showed a significant association between ErbB3 and ErbB2 expression and metastasis independent of tumor size. These results indicate that ErbB3-dependent signaling through ErbB3/ErbB2 heterodimers can contribute to metastasis through enhancing tumor cell invasion and intravasation in vivo and that ErbB-directed therapies may be useful for the inhibition of invasion independent of effects on tumor growth. (Cancer Res 2006; 66(3): 1418-26)

This article has been cited by other articles:

				B. Schoeberl, E. A. Pace, J. B. Fitzgerald, B. D. Harms, L. Xu, L. Nie, B. Linggi, A. Kalra, V. Paragas, R. Bukhalid, et al. Therapeutically Targeting ErbB3: A Key Node in Ligand-Induced Activation of the ErbB Receptor-PI3K Axis Sci. Signal., June 30, 2009; 2(77): ra31 - ra31. [Abstract] [Full Text] [PDF]

				D. Kedrin, J. Wyckoff, P. J. Boimel, S. J. Coniglio, N. E. Hynes, C. L. Arteaga, and J. E. Segall ERBB1 and ERBB2 Have Distinct Functions in Tumor Cell Invasion and Intravasation Clin. Cancer Res., June 1, 2009; 15(11): 3733 - 3739. [Abstract] [Full Text] [PDF]

				L. Hernandez, T. Smirnova, D. Kedrin, J. Wyckoff, L. Zhu, E. R. Stanley, D. Cox, W. J. Muller, J. W. Pollard, N. Van Rooijen, et al. The EGF/CSF-1 Paracrine Invasion Loop Can Be Triggered by Heregulin {beta}1 and CXCL12 Cancer Res., April 1, 2009; 69(7): 3221 - 3227. [Abstract] [Full Text] [PDF]

				J. Pu, C. D. McCaig, L. Cao, Z. Zhao, J. E. Segall, and M. Zhao EGF receptor signalling is essential for electric-field-directed migration of breast cancer cells J. Cell Sci., October 1, 2007; 120(19): 3395 - 3403. [Abstract] [Full Text] [PDF]

				S. Ollier, C. Robert-Granie, L. Bernard, Y. Chilliard, and C. Leroux Mammary Transcriptome Analysis of Food-Deprived Lactating Goats Highlights Genes Involved in Milk Secretion and Programmed Cell Death J. Nutr., March 1, 2007; 137(3): 560 - 567. [Abstract] [Full Text] [PDF]

				V. Folgiero, R. E. Bachelder, G. Bon, A. Sacchi, R. Falcioni, and A. M. Mercurio The {alpha}6{beta}4 Integrin Can Regulate ErbB-3 Expression: Implications for {alpha}6{beta}4 Signaling and Function Cancer Res., February 15, 2007; 67(4): 1645 - 1652. [Abstract] [Full Text] [PDF]

				L. Yen, Z. Cao, X. Wu, E. R.Q. Ingalla, C. Baron, L. J.T. Young, J. P. Gregg, R. D. Cardiff, A. D. Borowsky, C. Sweeney, et al. Loss of Nrdp1 Enhances ErbB2/ErbB3-Dependent Breast Tumor Cell Growth Cancer Res., December 1, 2006; 66(23): 11279 - 11286. [Abstract] [Full Text] [PDF]