Fes tyrosine kinase expression in the tumor niche correlates with enhanced tumor growth, angiogenesis, circulating tumor cells, metastasis, and infiltrating macrophages

Shengnan Zhang, Violeta Chitu, E. Richard Stanley, Bruce E. Elliott, Peter A. Greer

Research output: Contribution to journalArticle

16 Scopus citations

Abstract

Fes is a protein tyrosine kinase with cell autonomous oncogenic activities that are well established in cell culture and animal models, but its involvement in human cancer has been unclear. Abundant expression of Fes in vascular endothelial cells and myeloid cell lineages prompted us to explore roles for Fes in the tumor microenvironment. In an orthotopic mouse model of breast cancer, we found that loss of Fes in the host correlated with reductions in engrafted tumor growth rates, metastasis, and circulating tumor cells. The tumor microenvironment in Fes-deficient mice also showed reduced vascularity and fewer macrophages. In co-culture with tumor cells, Fes-deficient macrophages also poorly promoted tumor cell invasive behavior. Taken together, our observations argue that Fes inhibition might provide therapeutic benefits in breast cancer, in part by attenuating tumor-associated angiogenesis and the metastasis-promoting functions of tumor-associated macrophages.

Original languageEnglish (US)
Pages (from-to)1465-1473
Number of pages9
JournalCancer Research
Volume71
Issue number4
DOIs
Publication statusPublished - Feb 15 2011

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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