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

被引:1113
作者
Bhowmick, NA
Chytil, A
Plieth, D
Gorska, AE
Dumont, N
Shappell, S
Washington, MK
Neilson, EG
Moses, HL [1 ]
机构
[1] Vanderbilt Univ, Sch Med, Dept Canc Biol, Nashville, TN 37232 USA
[2] Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37232 USA
[3] Vanderbilt Univ, Sch Med, Dept Pathol, Nashville, TN 37232 USA
[4] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Nashville, TN 37232 USA
关键词
D O I
10.1126/science.1090922
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 (Tgfbr2(fspKO)). 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.
引用
收藏
页码:848 / 851
页数:4
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