FGFR3-expressing smooth muscle-like stromal cells differentiate in response to FGFR2IIIb-expressing prostate tumor cells and delay tumor progression

Chengliu Jin, Chaofeng Yang, Xiaochong Wu, Fen Wang, Wallace L. McKeehan

Research output: Contribution to journalArticle

2 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)500-505
Number of pages6
JournalIn Vitro Cellular and Developmental Biology - Animal
Volume47
Issue number7
DOIs
StatePublished - Aug 2011
Externally publishedYes

Keywords

  • Cell-cell communication
  • Dunning tumors
  • Prostate cancer
  • Receptor tyrosine kinases
  • Stromal-epithelial interactions
  • Tissue homeostasis
  • Tumor microenvironment

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'FGFR3-expressing smooth muscle-like stromal cells differentiate in response to FGFR2IIIb-expressing prostate tumor cells and delay tumor progression'. Together they form a unique fingerprint.

Cite this