A critical role for the inflammatory response in a mouse model of preneoplastic progression

Kathryn L. Schwertfeger, Wa Xian, Alan M. Kaplan, Sandra H. Burnett, Donald A. Cohen, Jeffrey M. Rosen

Research output: Contribution to journalArticle

54 Citations (Scopus)

Abstract

The tumor microenvironment, which includes inflammatory cells, vasculature, extracellular matrix, and fibroblasts, is a critical mediator of neoplastic progression and metastasis. Using an inducible transgenic mouse model of preneoplastic progression in the mammary gland, we discovered that activation of inducible fibroblast growth factor receptor-1 (iFGFR1) in the mammary epithelium rapidly increased the expression of several genes involved in the inflammatory response. Further analysis revealed that iFGFR1 activation induced recruitment of macrophages to the epithelium and continued association with the alveolar hyperplasias that developed following long-term activation. Studies using HC-11 mammary epithelial cells showed that iFGFR1-induced expression of the macrophage chemoattractant osteopontin was required for macrophage recruitment in vitro. Finally, conditional depletion of macrophages inhibited iFGFR1-mediated epithelial cell proliferation and lateral budding. These findings show that inflammatory cells, specifically macrophages, are critical for mediating early events in an inducible transgenic mouse model of preneoplastic progression.

Original languageEnglish (US)
Pages (from-to)5676-5685
Number of pages10
JournalCancer Research
Volume66
Issue number11
DOIs
StatePublished - Jun 1 2006

Fingerprint

Receptor, Fibroblast Growth Factor, Type 1
Macrophages
Transgenic Mice
Breast
Epithelium
Epithelial Cells
Osteopontin
Tumor Microenvironment
Chemotactic Factors
Human Mammary Glands
Hyperplasia
Extracellular Matrix
Fibroblasts
Cell Proliferation
Neoplasm Metastasis
Gene Expression

Cite this

A critical role for the inflammatory response in a mouse model of preneoplastic progression. / Schwertfeger, Kathryn L.; Xian, Wa; Kaplan, Alan M.; Burnett, Sandra H.; Cohen, Donald A.; Rosen, Jeffrey M.

In: Cancer Research, Vol. 66, No. 11, 01.06.2006, p. 5676-5685.

Research output: Contribution to journalArticle

Schwertfeger, Kathryn L. ; Xian, Wa ; Kaplan, Alan M. ; Burnett, Sandra H. ; Cohen, Donald A. ; Rosen, Jeffrey M. / A critical role for the inflammatory response in a mouse model of preneoplastic progression. In: Cancer Research. 2006 ; Vol. 66, No. 11. pp. 5676-5685.
@article{d76b0bb021c54e77841c1e839d568b9b,
title = "A critical role for the inflammatory response in a mouse model of preneoplastic progression",
abstract = "The tumor microenvironment, which includes inflammatory cells, vasculature, extracellular matrix, and fibroblasts, is a critical mediator of neoplastic progression and metastasis. Using an inducible transgenic mouse model of preneoplastic progression in the mammary gland, we discovered that activation of inducible fibroblast growth factor receptor-1 (iFGFR1) in the mammary epithelium rapidly increased the expression of several genes involved in the inflammatory response. Further analysis revealed that iFGFR1 activation induced recruitment of macrophages to the epithelium and continued association with the alveolar hyperplasias that developed following long-term activation. Studies using HC-11 mammary epithelial cells showed that iFGFR1-induced expression of the macrophage chemoattractant osteopontin was required for macrophage recruitment in vitro. Finally, conditional depletion of macrophages inhibited iFGFR1-mediated epithelial cell proliferation and lateral budding. These findings show that inflammatory cells, specifically macrophages, are critical for mediating early events in an inducible transgenic mouse model of preneoplastic progression.",
author = "Schwertfeger, {Kathryn L.} and Wa Xian and Kaplan, {Alan M.} and Burnett, {Sandra H.} and Cohen, {Donald A.} and Rosen, {Jeffrey M.}",
year = "2006",
month = "6",
day = "1",
doi = "10.1158/0008-5472.CAN-05-3781",
language = "English (US)",
volume = "66",
pages = "5676--5685",
journal = "Cancer Research",
issn = "0008-5472",
number = "11",

}

TY - JOUR

T1 - A critical role for the inflammatory response in a mouse model of preneoplastic progression

AU - Schwertfeger, Kathryn L.

AU - Xian, Wa

AU - Kaplan, Alan M.

AU - Burnett, Sandra H.

AU - Cohen, Donald A.

AU - Rosen, Jeffrey M.

PY - 2006/6/1

Y1 - 2006/6/1

N2 - The tumor microenvironment, which includes inflammatory cells, vasculature, extracellular matrix, and fibroblasts, is a critical mediator of neoplastic progression and metastasis. Using an inducible transgenic mouse model of preneoplastic progression in the mammary gland, we discovered that activation of inducible fibroblast growth factor receptor-1 (iFGFR1) in the mammary epithelium rapidly increased the expression of several genes involved in the inflammatory response. Further analysis revealed that iFGFR1 activation induced recruitment of macrophages to the epithelium and continued association with the alveolar hyperplasias that developed following long-term activation. Studies using HC-11 mammary epithelial cells showed that iFGFR1-induced expression of the macrophage chemoattractant osteopontin was required for macrophage recruitment in vitro. Finally, conditional depletion of macrophages inhibited iFGFR1-mediated epithelial cell proliferation and lateral budding. These findings show that inflammatory cells, specifically macrophages, are critical for mediating early events in an inducible transgenic mouse model of preneoplastic progression.

AB - The tumor microenvironment, which includes inflammatory cells, vasculature, extracellular matrix, and fibroblasts, is a critical mediator of neoplastic progression and metastasis. Using an inducible transgenic mouse model of preneoplastic progression in the mammary gland, we discovered that activation of inducible fibroblast growth factor receptor-1 (iFGFR1) in the mammary epithelium rapidly increased the expression of several genes involved in the inflammatory response. Further analysis revealed that iFGFR1 activation induced recruitment of macrophages to the epithelium and continued association with the alveolar hyperplasias that developed following long-term activation. Studies using HC-11 mammary epithelial cells showed that iFGFR1-induced expression of the macrophage chemoattractant osteopontin was required for macrophage recruitment in vitro. Finally, conditional depletion of macrophages inhibited iFGFR1-mediated epithelial cell proliferation and lateral budding. These findings show that inflammatory cells, specifically macrophages, are critical for mediating early events in an inducible transgenic mouse model of preneoplastic progression.

UR - http://www.scopus.com/inward/record.url?scp=33745260929&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33745260929&partnerID=8YFLogxK

U2 - 10.1158/0008-5472.CAN-05-3781

DO - 10.1158/0008-5472.CAN-05-3781

M3 - Article

VL - 66

SP - 5676

EP - 5685

JO - Cancer Research

JF - Cancer Research

SN - 0008-5472

IS - 11

ER -