title: Oncostatin M promotes mesenchymal stem cell-stimulated tumor growth through a paracrine mechanism involving periostin and TGFBI.
abstract: Oncostatin M, a member of the interleukin-6 family of cytokines, has been implicated in tumorigenesis of human prostate cancer. In the current study, we demonstrate that oncostatin M promotes human adipose tissue-derived mesenchymal stem cell-stimulated tumor growth in an in vivo xenograft transplantation model of the human prostate cancer cell line PC-3M-luc-C6, a PC3M cell line expressing the luciferase gene. Conditioned medium derived from oncostatin M-treated mesenchymal stem cells stimulated adhesion of PC-3M-luc-C6 cells. We identified TGFBI and periostin, extracellular matrix proteins implicated in tumorigenesis and metastasis, as oncostatin M-induced secreted proteins in mesenchymal stem cells. Treatment with oncostatin M stimulated secretion of periostin and TGFBI from mesenchymal stem cells in a time-dependent manner. Immunodepletion of TGFBI and periostin from conditioned medium derived from oncostatin M-treated mesenchymal stem cells resulted in abrogation of adhesion of PC-3M-luc-C6 cells stimulated by oncostatin M-conditioned medium. In addition, small interfering RNA-mediated silencing of TGFBI and periostin resulted in abrogation of cell adhesion stimulated by oncostatin M-conditioned medium. These results suggest that mesenchymal stem cell-derived TGFBI and periostin play a key role in tumorigenesis by stimulating adhesion of prostate cancer cells.
authors.affiliation: Medical Research Center for Ischemic Tissue Regeneration & Medical Research Institute, Yangsan 626-870, Gyeongsangnam-do, Republic of Korea.
authors.forename: Mi Jeong
authors.initials: MJ
authors.lastname: Lee
authors.forename: Soon Chul
authors.initials: SC
authors.lastname: Heo
authors.forename: Sang Hun
authors.initials: SH
authors.lastname: Shin
authors.forename: Yang Woo
authors.initials: YW
authors.lastname: Kwon
authors.forename: Eun Kyoung
authors.initials: EK
authors.lastname: Do
authors.forename: Dong-Soo
authors.initials: DS
authors.lastname: Suh
authors.forename: Man-Soo
authors.initials: MS
authors.lastname: Yoon
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000273:Adipose Tissue / Q000166:cytology; D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000378:metabolism*; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008819:Mice, Nude; D053683:Oncostatin M / Q000494:pharmacology*; D019899:Paracrine Communication / Q000187:drug effects*; D011471:Prostatic Neoplasms / Q000473:pathology*; D034741:RNA, Small Interfering / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D033581:Stem Cell Transplantation; D016212:Transforming Growth Factor beta / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays; D000099222:betaIG-H3 Protein
chemical_list: D015815:Cell Adhesion Molecules; D017077:Culture Media, Conditioned; D016326:Extracellular Matrix Proteins; D053683:Oncostatin M; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein; C512835:POSTN protein, human
keywords: GAPDH; MSCs; Mesenchymal stem cells; OSM; OSM CM; PBS; Periostin; Prostate cancer; SDF-1; TGFBI; conditioned medium from OSM-treated hASCs; glyceraldehyde-3-phosphate dehydrogenase; hASCs; human adipose tissue-derived MSCs; mesenchymal stem cells; oncostatin M; phosphate-buffered saline; siRNA; small interfering RNA; stromal cell-derived factor-1