Fibrosis and cancer: Do myofibroblasts come also from epithelial cells via EMT?

Derek C. Radisky, Paraic A. Kenny, Mina J. Bissell

Research output: Contribution to journalArticle

233 Citations (Scopus)

Abstract

Myofibroblasts produce and modify the extracellular matrix (ECM), secrete angiogenic and proinflammatory factors, and stimulate epithelial cell proliferation and invasion. Myofibroblasts are normally induced transiently during wound healing, but inappropriate induction of myofibroblasts causes organ fibrosis, which greatly enhances the risk of subsequent cancer development. As myofibroblasts are also found in the reactive tumor stroma, the processes involved in their development and activation are an area of active investigation. Emerging evidence suggests that a major source of fibrosis- and tumor-associated myofibroblasts is through transdifferentiation from non-malignant epithelial or epithelial-derived carcinoma cells through epithelial-mesenchymal transition (EMT). This review will focus on the role of EMT in fibrosis, considered in the context of recent studies showing that exposure of epithelial cells to matrix metalloproteinases (MMPs) can lead to increased levels of cellular reactive oxygen species (ROS) that stimulate transdifferentiation to myofibroblast-like cells. As deregulated MMP expression and increased cellular ROS are characteristic of both fibrosisand malignancy, these studies suggest that increased MMP expression may stimulate fibrosis, tumorigenesis, and tumor progression by inducing a specialized EMT in which epithelial cells transdifferentiate into activated myofibroblasts. This connection provides a new perspective on the development of the fibrosis and tumor microenvironments.

Original languageEnglish (US)
Pages (from-to)830-839
Number of pages10
JournalJournal of Cellular Biochemistry
Volume101
Issue number4
DOIs
StatePublished - Jul 1 2007
Externally publishedYes

Fingerprint

Epithelial-Mesenchymal Transition
Myofibroblasts
Tumors
Fibrosis
Epithelial Cells
Matrix Metalloproteinases
Reactive Oxygen Species
Neoplasms
Angiogenesis Inducing Agents
Cell proliferation
Chemical activation
Cells
Tumor Microenvironment
Wound Healing
Extracellular Matrix
Carcinogenesis
Cell Proliferation
Carcinoma

Keywords

  • Epithelial-mesenchymal transition
  • Extracellular matrix
  • Matrix metalloproteinases
  • Tumor microenvironment

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

Fibrosis and cancer : Do myofibroblasts come also from epithelial cells via EMT? / Radisky, Derek C.; Kenny, Paraic A.; Bissell, Mina J.

In: Journal of Cellular Biochemistry, Vol. 101, No. 4, 01.07.2007, p. 830-839.

Research output: Contribution to journalArticle

Radisky, Derek C. ; Kenny, Paraic A. ; Bissell, Mina J. / Fibrosis and cancer : Do myofibroblasts come also from epithelial cells via EMT?. In: Journal of Cellular Biochemistry. 2007 ; Vol. 101, No. 4. pp. 830-839.
@article{bae9055115e0420481a650e30259a707,
title = "Fibrosis and cancer: Do myofibroblasts come also from epithelial cells via EMT?",
abstract = "Myofibroblasts produce and modify the extracellular matrix (ECM), secrete angiogenic and proinflammatory factors, and stimulate epithelial cell proliferation and invasion. Myofibroblasts are normally induced transiently during wound healing, but inappropriate induction of myofibroblasts causes organ fibrosis, which greatly enhances the risk of subsequent cancer development. As myofibroblasts are also found in the reactive tumor stroma, the processes involved in their development and activation are an area of active investigation. Emerging evidence suggests that a major source of fibrosis- and tumor-associated myofibroblasts is through transdifferentiation from non-malignant epithelial or epithelial-derived carcinoma cells through epithelial-mesenchymal transition (EMT). This review will focus on the role of EMT in fibrosis, considered in the context of recent studies showing that exposure of epithelial cells to matrix metalloproteinases (MMPs) can lead to increased levels of cellular reactive oxygen species (ROS) that stimulate transdifferentiation to myofibroblast-like cells. As deregulated MMP expression and increased cellular ROS are characteristic of both fibrosisand malignancy, these studies suggest that increased MMP expression may stimulate fibrosis, tumorigenesis, and tumor progression by inducing a specialized EMT in which epithelial cells transdifferentiate into activated myofibroblasts. This connection provides a new perspective on the development of the fibrosis and tumor microenvironments.",
keywords = "Epithelial-mesenchymal transition, Extracellular matrix, Matrix metalloproteinases, Tumor microenvironment",
author = "Radisky, {Derek C.} and Kenny, {Paraic A.} and Bissell, {Mina J.}",
year = "2007",
month = "7",
day = "1",
doi = "10.1002/jcb.21186",
language = "English (US)",
volume = "101",
pages = "830--839",
journal = "Journal of Cellular Biochemistry",
issn = "0730-2312",
publisher = "Wiley-Liss Inc.",
number = "4",

}

TY - JOUR

T1 - Fibrosis and cancer

T2 - Do myofibroblasts come also from epithelial cells via EMT?

AU - Radisky, Derek C.

AU - Kenny, Paraic A.

AU - Bissell, Mina J.

PY - 2007/7/1

Y1 - 2007/7/1

N2 - Myofibroblasts produce and modify the extracellular matrix (ECM), secrete angiogenic and proinflammatory factors, and stimulate epithelial cell proliferation and invasion. Myofibroblasts are normally induced transiently during wound healing, but inappropriate induction of myofibroblasts causes organ fibrosis, which greatly enhances the risk of subsequent cancer development. As myofibroblasts are also found in the reactive tumor stroma, the processes involved in their development and activation are an area of active investigation. Emerging evidence suggests that a major source of fibrosis- and tumor-associated myofibroblasts is through transdifferentiation from non-malignant epithelial or epithelial-derived carcinoma cells through epithelial-mesenchymal transition (EMT). This review will focus on the role of EMT in fibrosis, considered in the context of recent studies showing that exposure of epithelial cells to matrix metalloproteinases (MMPs) can lead to increased levels of cellular reactive oxygen species (ROS) that stimulate transdifferentiation to myofibroblast-like cells. As deregulated MMP expression and increased cellular ROS are characteristic of both fibrosisand malignancy, these studies suggest that increased MMP expression may stimulate fibrosis, tumorigenesis, and tumor progression by inducing a specialized EMT in which epithelial cells transdifferentiate into activated myofibroblasts. This connection provides a new perspective on the development of the fibrosis and tumor microenvironments.

AB - Myofibroblasts produce and modify the extracellular matrix (ECM), secrete angiogenic and proinflammatory factors, and stimulate epithelial cell proliferation and invasion. Myofibroblasts are normally induced transiently during wound healing, but inappropriate induction of myofibroblasts causes organ fibrosis, which greatly enhances the risk of subsequent cancer development. As myofibroblasts are also found in the reactive tumor stroma, the processes involved in their development and activation are an area of active investigation. Emerging evidence suggests that a major source of fibrosis- and tumor-associated myofibroblasts is through transdifferentiation from non-malignant epithelial or epithelial-derived carcinoma cells through epithelial-mesenchymal transition (EMT). This review will focus on the role of EMT in fibrosis, considered in the context of recent studies showing that exposure of epithelial cells to matrix metalloproteinases (MMPs) can lead to increased levels of cellular reactive oxygen species (ROS) that stimulate transdifferentiation to myofibroblast-like cells. As deregulated MMP expression and increased cellular ROS are characteristic of both fibrosisand malignancy, these studies suggest that increased MMP expression may stimulate fibrosis, tumorigenesis, and tumor progression by inducing a specialized EMT in which epithelial cells transdifferentiate into activated myofibroblasts. This connection provides a new perspective on the development of the fibrosis and tumor microenvironments.

KW - Epithelial-mesenchymal transition

KW - Extracellular matrix

KW - Matrix metalloproteinases

KW - Tumor microenvironment

UR - http://www.scopus.com/inward/record.url?scp=34447250376&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34447250376&partnerID=8YFLogxK

U2 - 10.1002/jcb.21186

DO - 10.1002/jcb.21186

M3 - Article

C2 - 17211838

AN - SCOPUS:34447250376

VL - 101

SP - 830

EP - 839

JO - Journal of Cellular Biochemistry

JF - Journal of Cellular Biochemistry

SN - 0730-2312

IS - 4

ER -