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Cited by 127TGF-β signaling in diseasesCancer Cells and MetastasisLiver physiology and pathology

Cancer associated fibroblasts stimulated by transforming growth factor beta1 (TGF-β1) increase invasion rate of tumor cells: a population study

Casey, Theresa M., Eneman, Jonathan, Crocker, Abigail, White, Jeffrey, Tessitore, Joseph, Stanley, Mary, Harlow, Seth, Bunn, Janice Y. +3 more·2008·Breast Cancer Research and Treatment
DOI 10.1007/s10549-007-9684-7
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Abstract

Cancer associated fibroblasts (CAFs) are believed to promote tumor growth and progression. Our objective was to measure the effect of TGF-beta1 on fibroblasts isolated from invasive breast cancer patients. Fibroblasts were isolated from tissue obtained at surgery from patients with invasive breast cancer (CAF; n = 28) or normal reduction mammoplasty patients (normal; n = 10). Myofibroblast activation was measured by counting cells immunostained for smooth muscle alpha actin (ACTA2) in cultures +/- TGF-beta 1. Conditioned media (CM) was collected for invasion assays and RNA was isolated from cultures incubated in media +/- TGF-beta1 for 24 h. Q-PCR was used to measure expression of cyclin D1, fibronectin, laminin, collagen I, urokinase, stromelysin-1, and ACTA2 genes. Invasion rate was measured in chambers plated with MDA-MB-231 cells and exposed to CM in the bottom chamber; the number of cells that invaded into the bottom chamber was counted. Wilcox Rank Sum tests were used to evaluate differences in CAFs and normal fibroblasts and the effect of TGF-beta 1. There was no difference in percent myofibroblasts or invasion rate between normal and CAF cultures. However, TGF-beta1 significantly increased the percent of myofibroblasts (P < 0.01) and invasion rate (P = 0.02) in CAF cultures. Stromelysin-1 expression was significantly higher in normal versus CAF cultures (P < 0.01). TGF-beta 1 significantly increased ACTA2 expression in both normal and CAF cultures (P < 0.01). Expression of fibronectin and laminin was significantly increased by TGF-beta in CAF cultures (P < 0.01). CAFs were measurably different from normal fibroblasts in response to TGF-beta 1, suggesting that TGF-beta stimulates changes in CAFs that foster tumor invasion.

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  • The αSMA-high, matrix-producing-high state is reversible, supported by the responsiveness of matrix production and the αSMA promoter to extracellular cues including substrate stiffness.

    “the responsiveness of matrix production by fibroblasts and the αSMA promoter to a range of extracellular cues, including substrate stiffness, supports the idea that the αSMA-high, matrix producing-high state is reversible63,64,137–139.”

    From A framework for advancing our understanding of cancer-associated fibroblasts (2020) · cites this paper as [139]

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Authors
Casey, T. M., Eneman, J., Crocker, A., White, J., Tessitore, J., Stanley, M., Harlow, S., Bunn, J. Y., Weaver, D., Muss, H., & Plaut, K.
Affiliations
  • Michigan State University (US)
  • University of Vermont (US)
Corresponding author
Casey, Theresa M.
ORCID
Venue
Breast Cancer Research and Treatment
Publisher
Springer Science and Business Media LLC
Published
2007-08-03
Volume
110
Issue
1
Pages
39-49
ISSN
  • 0167-6806 (ISSN-L)
  • 1573-7217
DOI
10.1007/s10549-007-9684-7
OpenAlex
W2061346823
Cited by
127
References
3
Citations by year
2026: 2 · 2025: 5 · 2024: 6 · 2023: 5 · 2022: 8 · 2021: 9 · 2020: 9 · 2019: 8 · 2018: 4 · 2017: 7 · 2016: 6 · 2015: 6 · 2014: 8 · 2013: 12 · 2012: 7
FWCI
1.59
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (tdm)
Locations
  • Breast Cancer Research and Treatment (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Cancer Institute (P30CA022435, P30-CA 22435)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
  • Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Keywords
cancer-associated fibroblasts, TGF-β1, tumor invasion, breast cancer, myofibroblast activation, smooth muscle actin, stromelysin-1, fibronectin, laminin, type I collagen, urokinase, conditioned medium, MDA-MB-231 cells, tumor microenvironment
MeSH terms
Adult, Aged, Aged, 80 and over, Breast Neoplasms, Female, Fibroblasts, Humans, Middle Aged, Neoplasm Invasiveness, Urokinase-Type Plasminogen Activator, Matrix Metalloproteinase 3, Transforming Growth Factor beta1

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