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TGF-beta signaling in fibroblasts modulates the oncogenic potential of adjacent epithelia

Neil A Bhowmick1, Anna Chytil, David Plieth

  • 1Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.

Science (New York, N.Y.)
|February 7, 2004
PubMed

Insights

Transforming growth factor-beta (TGF-beta) signaling in fibroblasts influences cancer development in nearby epithelial tissues. Disrupting this signaling promotes epithelial cell growth and tumor formation, highlighting its role in cancer progression.

Area of Science:

  • Oncology
  • Cell Biology
  • Molecular Biology

Background:

  • Stromal cells significantly influence the carcinogenic process in adjacent epithelia.
  • Epithelial-mesenchymal interactions are critical in cancer development.
  • Transforming growth factor-beta (TGF-beta) signaling plays a key role in these interactions.

Purpose of the Study:

  • To determine the role of TGF-beta signaling in fibroblasts on epithelial carcinogenesis.
  • To investigate the effects of conditional inactivation of the TGF-beta type II receptor gene in mouse fibroblasts (Tgfbr2fspKO).

Main Methods:

  • Conditional inactivation of the TGF-beta type II receptor gene in mouse fibroblasts.
  • Analysis of epithelial and stromal compartments in prostate and forestomach tissues.
  • Assessment of signaling pathways, including hepatocyte growth factor (HGF).

Main Results:

  • Loss of TGF-beta responsiveness in fibroblasts led to intraepithelial neoplasia in the prostate.
  • Invasive squamous cell carcinoma of the forestomach was observed.
  • Both conditions were associated with an increased abundance of stromal cells.
  • Activation of paracrine hepatocyte growth factor (HGF) signaling was identified as a mechanism for epithelial proliferation.

Conclusions:

  • TGF-beta signaling in fibroblasts modulates the growth of adjacent epithelia.
  • Disruption of TGF-beta signaling in fibroblasts can promote oncogenic transformation in epithelial tissues.
  • Fibroblast-derived TGF-beta signaling is a critical regulator of tissue-specific carcinogenesis.

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