ErbB3-dependent motility and intravasation in breast cancer metastasis

Chengsen Xue, Fubo Liang, Radma Mahmood, Magalis Vuolo, Jeffrey Wyckoff, Hong Qian, Kun Lin Tsai, Mimi Kim, Joseph Locker, Zhong Yin Zhang, Jeffrey E. Segall

Research output: Contribution to journalArticle

66 Scopus citations

Abstract

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 β1. 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.

Original languageEnglish (US)
Pages (from-to)1418-1426
Number of pages9
JournalCancer Research
Volume66
Issue number3
DOIs
StatePublished - Feb 1 2006

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Xue, C., Liang, F., Mahmood, R., Vuolo, M., Wyckoff, J., Qian, H., Tsai, K. L., Kim, M., Locker, J., Zhang, Z. Y., & Segall, J. E. (2006). ErbB3-dependent motility and intravasation in breast cancer metastasis. Cancer Research, 66(3), 1418-1426. https://doi.org/10.1158/0008-5472.CAN-05-0550