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 Citations (Scopus)

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
StatePublished - Feb 15 2011

Fingerprint

Circulating Neoplastic Cells
Protein-Tyrosine Kinases
Macrophages
Neoplasm Metastasis
Growth
Neoplasms
Tumor Microenvironment
Breast Neoplasms
Cell Lineage
Myeloid Cells
Coculture Techniques
Endothelial Cells
Animal Models
Cell Culture Techniques

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Fes tyrosine kinase expression in the tumor niche correlates with enhanced tumor growth, angiogenesis, circulating tumor cells, metastasis, and infiltrating macrophages. / Zhang, Shengnan; Chitu, Violeta; Stanley, E. Richard; Elliott, Bruce E.; Greer, Peter A.

In: Cancer Research, Vol. 71, No. 4, 15.02.2011, p. 1465-1473.

Research output: Contribution to journalArticle

@article{a09bfd8398b54435ae4a32d3b53e0b91,
title = "Fes tyrosine kinase expression in the tumor niche correlates with enhanced tumor growth, angiogenesis, circulating tumor cells, metastasis, and infiltrating macrophages",
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.",
author = "Shengnan Zhang and Violeta Chitu and Stanley, {E. Richard} and Elliott, {Bruce E.} and Greer, {Peter A.}",
year = "2011",
month = "2",
day = "15",
doi = "10.1158/0008-5472.CAN-10-3757",
language = "English (US)",
volume = "71",
pages = "1465--1473",
journal = "Cancer Research",
issn = "0008-5472",
publisher = "American Association for Cancer Research Inc.",
number = "4",

}

TY - JOUR

T1 - Fes tyrosine kinase expression in the tumor niche correlates with enhanced tumor growth, angiogenesis, circulating tumor cells, metastasis, and infiltrating macrophages

AU - Zhang, Shengnan

AU - Chitu, Violeta

AU - Stanley, E. Richard

AU - Elliott, Bruce E.

AU - Greer, Peter A.

PY - 2011/2/15

Y1 - 2011/2/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=79951830119&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79951830119&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-10-3757

DO - 10.1158/0008-5472.CAN-10-3757

M3 - Article

C2 - 21159660

AN - SCOPUS:79951830119

VL - 71

SP - 1465

EP - 1473

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 4

ER -