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TGF-ß Signaling in Fibroblasts Modulates the Oncogenic Potential of Adjacent Epithelia
Neil A. Bhowmick,1,4Anna Chytil,1David Plieth,2Agnieszka E. Gorska,1,4Nancy Dumont,2,4Scott Shappell,3,4M. Kay Washington,3,4Eric G. Neilson,2,4Harold L. Moses1,3,4*
Stromal cells can have a significant impact on the carcinogenicprocess in adjacent epithelia. The role of transforming growthfactor–ß (TGF-ß) signaling in suchepithelial-mesenchymal interactions was determined by conditionalinactivation of the TGF-ß type II receptor gene inmouse fibroblasts (Tgfbr2fspKO). The loss of TGF-ßresponsiveness in fibroblasts resulted in intraepithelial neoplasiain 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) signalingwas identified as one possible mechanism for stimulation ofepithelial proliferation. Thus, TGF-ß signaling infibroblasts modulates the growth and oncogenic potential ofadjacent epithelia in selected tissues.
1 Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. 2 Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. 3 Department of Pathology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. 4 the Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
* To whom correspondence should be addressed. E-mail: hal.moses{at}vanderbilt.edu.
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