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: Mi Jeong Lee, Soon Chul Heo, Sang Hun Shin, Yang Woo Kwon, Eun Kyoung Do, Dong-Soo Suh, Man-Soo Yoon, Jae Ho Kim
• Journal: The international journal of biochemistry & cell biology (Int J Biochem Cell Biol) Vol. 45 Issue 8 Pg. 1869-77 (Aug 2013) ISSN: 1878-5875 [Electronic] Netherlands
• PMID: 23735324 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ltd. All rights reserved.

Chemical References

• Cell Adhesion Molecules
• Culture Media, Conditioned
• Extracellular Matrix Proteins
• POSTN protein, human
• RNA, Small Interfering
• Recombinant Proteins
• Transforming Growth Factor beta
• Oncostatin M
• betaIG-H3 protein

Topics

• Adipose Tissue (cytology)
• Animals
• Cell Adhesion (drug effects)
• Cell Adhesion Molecules (metabolism)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Culture Media, Conditioned (pharmacology)
• Extracellular Matrix Proteins (metabolism)
• Gene Silencing (drug effects)
• Humans
• Male
• Mesenchymal Stem Cells (cytology, drug effects, metabolism)
• Mice
• Mice, Nude
• Oncostatin M (pharmacology)
• Paracrine Communication (drug effects)
• Prostatic Neoplasms (pathology)
• RNA, Small Interfering (metabolism)
• Recombinant Proteins (pharmacology)
• Stem Cell Transplantation
• Transforming Growth Factor beta (metabolism)
• Xenograft Model Antitumor Assays