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Tumorigenesis

Nuisance neighbours

Nature Reviews Cancer volume 4, page 170 (2004)Cite this article

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It is well known that disrupting the normal interactions between epithelial cells and fibroblasts in the underlying stroma can lead to tumorigenesis, but the signalling pathways that are involved in this are poorly understood. To investigate a potential role of Tgf-β signalling in stroma–epithelium interactions, Moses and co-workers made transgenic mice in which the gene encoding the Tgf-β type II receptor (TGF-βRII) — a crucial component of Tgf-β signalling — is specifically inactivated in fibroblasts (Tgfbr2fspKO mice). Increased proliferation of both fibroblasts and epithelial cells was seen in prostate tissue from these mice, with prostate epithelial cells also showing neoplastic characteristics. In the forestomach, even more marked effects on epithelial cells were seen, with invasive squamous-cell carcinomas developing in 100% of Tgfbr2fspKO mice.

But how does loss of Tgf-β signalling in fibroblasts trigger tumorigenesis in adjacent epithelia? Hepatocyte growth factor (Hgf) is one target of Tgf-β signalling, so Moses and colleagues analysed Hgf signalling in Tgfbr2fspKO animals. Cultured fibroblasts from Tgfbr2fspKO mice were found to secrete three times as much of the active form of Hgf as cells from control mice. Furthermore, increased levels of the phosphorylated, active form of the Hgf receptor — c-Met — were seen in prostate and forestomach epithelial cells from Tgfbr2fspKO mice.

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References

ORIGINAL RESEARCH PAPER

  1. Bhowmick, N. A. et al. TGF-β signaling in fibroblasts modulates the oncogenic potential of adjacent epithelia. Science 303, 848–851 (2004)

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FURTHER READING

  1. Siegel, P. M. & Massagué, J. Cytostatic and apoptotic actions of TGF-β in homeostasis and cancer. Nature Rev. Cancer 3, 807–820 (2003)

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Authors
  1. Louisa Flintoft
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Flintoft, L. Nuisance neighbours. Nat Rev Cancer 4, 170 (2004). https://doi.org/10.1038/nrc1305

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  • DOI: https://doi.org/10.1038/nrc1305

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