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

Bhowmick NA, Chytil A, Plieth D, Gorska AE, Dumont N, Shappell S, Washington MK, Neilson EG, Moses HL
Science. 2004 303 (5659): 848-51

PMID: 14764882 · DOI:10.1126/science.1090922

Stromal cells can have a significant impact on the carcinogenic process in adjacent epithelia. The role of transforming growth factor-beta (TGF-beta) signaling in such epithelial-mesenchymal interactions was determined by conditional inactivation of the TGF-beta type II receptor gene in mouse fibroblasts (Tgfbr2fspKO). The loss of TGF-beta responsiveness in fibroblasts resulted in intraepithelial neoplasia in prostate and invasive squamous cell carcinoma of the forestomach, both associated with an increased abundance of stromal cells. Activation of paracrine hepatocyte growth factor (HGF) signaling was identified as one possible mechanism for stimulation of epithelial proliferation. Thus, TGF-beta signaling in fibroblasts modulates the growth and oncogenic potential of adjacent epithelia in selected tissues.

MeSH Terms (28)

Animals Carcinoma, Squamous Cell Cell Division Cells, Cultured Cell Transformation, Neoplastic Epithelial Cells Female Fibroblasts Gastric Mucosa Hepatocyte Growth Factor Male Mice Mice, Inbred C57BL Mice, Knockout Mice, Transgenic Neoplasms, Glandular and Epithelial Prostate Prostatic Intraepithelial Neoplasia Protein-Serine-Threonine Kinases Proto-Oncogene Proteins c-met Receptor, Transforming Growth Factor-beta Type II Receptors, Transforming Growth Factor beta Recombination, Genetic Signal Transduction Stomach Stomach Neoplasms Stromal Cells Transforming Growth Factor beta

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