title: Clear cell renal cell carcinoma induces fibroblast-mediated production of stromal periostin.
abstract: OBJECTIVE
  Increase in periostin (PN) was reported in clear cell renal cell carcinoma (ccRCC). But how PN contributes to ccRCC pathogenesis remains unclear. This research will investigate the underlying mechanism.
  
  
  METHODS
  The PN protein in 37 adjacent non-tumour kidney (ANK) tissues, their respective ccRCCs, 16 cases of metastasised ccRCC and xenograft tumours was analysed by immunohistochemistry. PN expression in ccRCC cells and NIH3T3 fibroblasts was examined by real time PCR (polymerase chain reaction) and western blot.
  
  
  RESULTS
  PN was detected at low levels in the tubular epithelial cells of ANKs. PN was robustly increased in the ccRCC-associated stroma of both organ-confined and metastasised ccRCCs. Furthermore, despite A498 ccRCC cells and their-derived xenograft tumour cells expressing a low level of PN, a strong presence of stromal PN was observed especially in the boundary region between xenograft tumour mass and non-tumour tissue. Collectively, these results suggest that the ccRCC-associated PN was derived from stroma instead of tumours. This notion was supported by the co-existence of PN with α-smooth muscle actin (αSMA), a marker of activated fibroblasts, in both local and metastasised ccRCC. Furthermore, co-culture of NIH3T3 mouse fibroblasts with either human A498 or 786-0 ccRCC cells dramatically enhanced PN transcription only in NIH3T3 cells as well as NIH3T3 cell-mediated accumulation of extracellular PN. In return, extracellular PN significantly enhanced A498 cell attachment. Elevation of PN promotes NIH3T3 cell proliferation and enhanced AKT activation.
  
  
  CONCLUSIONS
  ccRCC induces fibroblast-mediated accumulation of stromal PN; stromal PN enhances ccRCC cell attachment and fibroblast proliferation.
authors.affiliation: Division of Nephrology, Department of Medicine, St. Joseph's Hospital, Hamilton, Ontario, Canada; Department of Surgery, McMaster University, St. Joseph's Hospital, Hamilton, Ontario, Canada; Father Sean O'Sullivan Research Institute, St. Joseph's Hospital, Hamilton, Ontario, Canada; The Hamilton Center for Kidney Research, St. Joseph's Hospital, Hamilton, Ontario, Canada.
authors.forename: Nazihah
authors.initials: N
authors.lastname: Bakhtyar
authors.forename: Nicholas
authors.initials: N
authors.lastname: Wong
authors.forename: Anil
authors.initials: A
authors.lastname: Kapoor
authors.forename: Jean-Claude
authors.initials: JC
authors.lastname: Cutz
authors.forename: Brianne
authors.initials: B
authors.lastname: Hill
authors.forename: Michelle
authors.initials: M
authors.lastname: Ghert
authors.forename: Damu
authors.initials: D
authors.lastname: Tang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D002292:Carcinoma, Renal Cell / Q000235:genetics / Q000378:metabolism* / Q000556:secondary; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018920:Coculture Techniques; D004789:Enzyme Activation; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D057809:HEK293 Cells; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D008875:Middle Aged; D041681:NIH 3T3 Cells; D009368:Neoplasm Transplantation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism* / Q000473:pathology; D014162:Transfection; D015854:Up-Regulation
chemical_list: D015815:Cell Adhesion Molecules; C512835:POSTN protein, human; C082838:Postn protein, mouse; D051057:Proto-Oncogene Proteins c-akt
keywords: Periostin; Tumourigenesis; ccRCC