TGF-beta signaling in fibroblasts modulates the oncogenic potential of adjacent epithelia.
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.
Bhowmick
Neil A
NA
Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Chytil
Anna
A
Plieth
David
D
Gorska
Agnieszka E
AE
Dumont
Nancy
N
Shappell
Scott
S
Washington
M Kay
MK
Neilson
Eric G
EG
Moses
Harold L
HL
D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D002455:Cell Division; D002471:Cell Transformation, Neoplastic; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000502:physiology*; D005260:Female; D005347:Fibroblasts / Q000502:physiology*; D005753:Gastric Mucosa / Q000378:metabolism; D017228:Hepatocyte Growth Factor / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009375:Neoplasms, Glandular and Epithelial / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D011467:Prostate / Q000166:cytology / Q000378:metabolism / Q000473:pathology; D019048:Prostatic Intraepithelial Neoplasia / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D017346:Protein Serine-Threonine Kinases; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D015398:Signal Transduction; D013270:Stomach / Q000166:cytology / Q000473:pathology; D013274:Stomach Neoplasms / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D017154:Stromal Cells / Q000502:physiology*; D016212:Transforming Growth Factor beta / Q000502:physiology*
D018125:Receptors, Transforming Growth Factor beta; D016212:Transforming Growth Factor beta; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II