title: FGFR3-expressing smooth muscle-like stromal cells differentiate in response to FGFR2IIIb-expressing prostate tumor cells and delay tumor progression.
abstract: Evolution of unresponsiveness to homeostasis-promoting signals from the microenvironment is a hallmark of malignant tumor cells. In Dunning R3327 model rat prostate tumors that are comprised of distinct stromal and epithelial compartments, progression from non-malignant, androgen-responsive tumors to malignancy is characterized by loss of compartmentation coincident with a loss of resident epithelial cell FGFR2IIIb that receives instructive signals from stromal FGF7 and FGF10. Restoration of FGFR2IIIb to malignant tumor cells restores responsiveness to stromal cells, restores distinct stromal and epithelial compartments, and retards malignant progression. Cultured stromal cells from two-compartment tumors are comprised of smooth muscle α-actin-positive cells that express predominantly FGFR3 and fibroblast-like cells devoid of α-actin and FGFR3. Here, we show that it is primarily the smooth muscle cell-like α-actin-expressing stromal cells that survive, morphologically differentiate, and delay tumor incidence and size in the presence of malignant cells in which FGFR2IIIb has been restored. Expression of FGFR3 by transfection in the fibroblast-like stromal cells conferred ability to respond similar to the smooth muscle cell-like stromal cells in which FGFR3 is normally resident. These results highlight the importance of the two-way communication back and forth between stroma and epithelium that is mediated by signaling within the FGFR family during progression to malignancy.
authors.affiliation: Center for Cancer and Stem Cell Biology, Texas A&M Health Science Center, Institute of Biosciences and Technology, 2121 W. Holcombe Blvd., Houston, TX 77030-3303, USA.
authors.forename: Chengliu
authors.initials: C
authors.lastname: Jin
authors.forename: Chaofeng
authors.initials: C
authors.lastname: Yang
authors.forename: Xiaochong
authors.initials: X
authors.lastname: Wu
authors.forename: Fen
authors.initials: F
authors.lastname: Wang
authors.forename: Wallace L
authors.initials: WL
authors.lastname: McKeehan
mesh_terms: D000818:Animals; D018450:Disease Progression; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000166:cytology / Q000378:metabolism*; D009374:Neoplasms, Experimental; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051381:Rats; D051497:Receptor, Fibroblast Growth Factor, Type 2 / Q000235:genetics / Q000378:metabolism*; D051498:Receptor, Fibroblast Growth Factor, Type 3 / Q000235:genetics / Q000378:metabolism*; D017154:Stromal Cells / Q000473:pathology / Q000502:physiology*; D014407:Tumor Cells, Cultured
chemical_list: D020033:Protein Isoforms; D051497:Receptor, Fibroblast Growth Factor, Type 2; D051498:Receptor, Fibroblast Growth Factor, Type 3