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Updated: May 5, 2026

Experimental Generation of Carcinoma-Associated Fibroblasts CAFs from Human Mammary Fibroblasts
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Experimental Generation of Carcinoma-Associated Fibroblasts CAFs from Human Mammary Fibroblasts

Published on: October 25, 2011

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Tumour suppressor gene function in carcinoma-associated fibroblasts: from tumour cells via EMT and back again?

Lauren E Drake1, Kay F Macleod

  • 1Ben May Department for Cancer Research, University of Chicago, IL, USA; Committee on Molecular Pathogenesis and Molecular Medicine, University of Chicago, IL, USA.

The Journal of Pathology
|November 21, 2013
PubMed

Insights

Tumour suppressor gene inactivation in fibroblasts creates carcinoma-associated fibroblasts (CAFs) that promote cancer growth via signaling. CAFs may also originate from tumor cells through epithelial-mesenchymal transition (EMT).

Area of Science:

  • Oncology
  • Cancer Biology
  • Molecular Oncology

Background:

  • Inactivation of tumor suppressor genes like RB, TP53, and PTEN is observed in the stroma of various human cancers.
  • Mouse models confirm that deleting these tumor suppressors in fibroblasts transforms them into cancer-promoting carcinoma-associated fibroblasts (CAFs).

Purpose of the Study:

  • To explore the origins and mechanisms of carcinoma-associated fibroblast (CAF) generation in cancer.
  • To investigate the role of fibroblast genetic alterations and epithelial-mesenchymal transition (EMT) in CAF formation.

Main Methods:

  • Review of recent reports on tumor suppressor gene inactivation in cancer stroma.
  • Analysis of mouse models demonstrating fibroblast-to-CAF conversion upon tumor suppressor deletion.
  • Examination of lineage-tracing studies investigating CAF origins.

Main Results:

  • Loss of RB, TP53, or PTEN in fibroblasts leads to CAF phenotypes with tumor-promoting paracrine signaling.
  • CAFs secrete growth factors, chemokines, and MMPs that enhance tumor cell activity.
  • Evidence suggests CAFs can arise independently of tumor cell genetics, but also potentially from tumor cells via EMT.

Conclusions:

  • Fibroblast genetic alterations, particularly tumor suppressor inactivation, are a key driver of CAF formation and pro-tumorigenic activity.
  • The potential for tumor cells to differentiate into CAFs through EMT represents an alternative source of CAFs, warranting further investigation in vivo.
Keywords:
EMTPtenRBTGFβcarcinoma-associated fibroblastslineage tracingmicro-RNAsp53trophic support

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