Epidermal growth factor receptor overexpression results in increased tumor cell motility in vivo coordinately with enhanced intravasation and metastasis

Chengsen Xue, Jeffrey Wyckoff, Fubo Liang, Mazen Sidani, Stefania Violini, Kun Lin Tsai, Zhong Yin Zhang, Erik Sahai, John S. Condeelis, Jeffrey E. Segall

Research output: Contribution to journalArticle

144 Citations (Scopus)

Abstract

Although overexpression of the epidermal growth factor receptor (EGFR; ErbB1) has been correlated with poor prognosis in breast and other cancers, clinical trials of ErbB1 inhibitors have shown limited efficacy in inhibiting tumor proliferation. To evaluate other possible roles of ErbB1 in tumor malignancy besides proliferation, we have developed a series of tools for analysis of intravasation. Overexpression of ErbB1 in MTLn3 mammary adenocarcinoma cells results in increased intravasation and lung metastasis from tumors formed by injection of cells in the mammary fat pad. However, increased ErbB1 expression has no effect on primary tumor growth and lung seeding efficiency of cells injected i.v. Chemotactic responses to low concentrations of EGF in vitro and cell motility in vivo in the primary tumor measured using intravital imaging are significantly increased by ErbB1 overexpression. The increased cell motility is restricted to ErbB1-overexpressing cells in tumors containing mixtures of cells expressing different ErbB1 levels, arguing for a cell-autonomous effect of increased ErbB1 expression rather than alteration of the tumor microenvironment. In summary, we propose that ErbB1 overexpression makes more significant contributions to intravasation than growth in some tumors and present a novel model for studying ErbB1 contributions to tumor metastasis via chemotaxis and intravasation.

Original languageEnglish (US)
Pages (from-to)192-197
Number of pages6
JournalCancer Research
Volume66
Issue number1
DOIs
StatePublished - Jan 1 2006

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Epidermal Growth Factor Receptor
Cell Movement
Neoplasm Metastasis
Neoplasms
Breast
Lung
Tumor Microenvironment
Chemotaxis
Growth
Epidermal Growth Factor
Adipose Tissue
Adenocarcinoma
Clinical Trials
Breast Neoplasms
Injections

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Epidermal growth factor receptor overexpression results in increased tumor cell motility in vivo coordinately with enhanced intravasation and metastasis. / Xue, Chengsen; Wyckoff, Jeffrey; Liang, Fubo; Sidani, Mazen; Violini, Stefania; Tsai, Kun Lin; Zhang, Zhong Yin; Sahai, Erik; Condeelis, John S.; Segall, Jeffrey E.

In: Cancer Research, Vol. 66, No. 1, 01.01.2006, p. 192-197.

Research output: Contribution to journalArticle

Xue, Chengsen ; Wyckoff, Jeffrey ; Liang, Fubo ; Sidani, Mazen ; Violini, Stefania ; Tsai, Kun Lin ; Zhang, Zhong Yin ; Sahai, Erik ; Condeelis, John S. ; Segall, Jeffrey E. / Epidermal growth factor receptor overexpression results in increased tumor cell motility in vivo coordinately with enhanced intravasation and metastasis. In: Cancer Research. 2006 ; Vol. 66, No. 1. pp. 192-197.
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