title: Periostin mediates human adipose tissue-derived mesenchymal stem cell-stimulated tumor growth in a xenograft lung adenocarcinoma model.
abstract: Mesenchymal stem cells stimulate tumor growth in vivo through a lysophosphatidic acid (LPA)-dependent mechanism. However, the molecular mechanism by which mesenchymal stem cells stimulate tumorigenesis is largely elusive. In the present study, we demonstrate that conditioned medium from A549 human lung adenocarcinoma cells (A549 CM) induces expression of periostin, an extracellular matrix protein, in human adipose tissue-derived mesenchymal stem cells (hASCs). A549 CM-stimulated periostin expression was abrogated by pretreatment of hASCs with the LPA receptor 1 (LPA(1)) inhibitor Ki16425 or short hairpin RNA-mediated silencing of LPA(1), suggesting a key role of the LPA-LPA(1) signaling axis in A549 CM-stimulated periostin expression. Using a xenograft transplantation model of A549 cells, we demonstrated that co-injection of hASCs potentiated tumor growth of A549 cells in vivo and that co-transplanted hASCs expressed not only periostin but also α-smooth muscle actin (α-SMA), a marker of carcinoma-associated fibroblasts. Small interfering RNA- or short hairpin RNA-mediated silencing of periostin resulted in blockade of LPA-induced α-SMA expression in hASCs. In addition, silencing of periostin resulted in blockade of hASC-stimulated growth of A549 xenograft tumors and in vivo differentiation of transplanted hASCs to α-SMA-positive carcinoma-associated fibroblasts. Conditioned medium derived from LPA-treated hASCs (LPA CM) potentiated proliferation and adhesion of A549 cells and short interfering RNA-mediated silencing or immunodepletion of periostin from LPA CM abrogated proliferation and adhesion of A549 cells. These results suggest a pivotal role for hASC-secreted periostin in growth of A549 xenograft tumors within the tumor microenvironment.
authors.affiliation: Medical Research Center for Ischemic Tissue Regeneration, Pusan National University, Yangsan, Republic of Korea.
authors.forename: Soon Chul
authors.initials: SC
authors.lastname: Heo
authors.forename: Kook One
authors.initials: KO
authors.lastname: Lee
authors.forename: Sang Hun
authors.initials: SH
authors.lastname: Shin
authors.forename: Yang Woo
authors.initials: YW
authors.lastname: Kwon
authors.forename: Young Mi
authors.initials: YM
authors.lastname: Kim
authors.forename: Chang Hun
authors.initials: CH
authors.lastname: Lee
authors.forename: Yeong Dae
authors.initials: YD
authors.lastname: Kim
authors.forename: Min Ki
authors.initials: MK
authors.lastname: Lee
authors.forename: Man-Soo
authors.initials: MS
authors.lastname: Yoon
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism / Q000473:pathology*; D000273:Adipose Tissue / Q000473:pathology*; D000818:Animals; D015153:Blotting, Western; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D049109:Cell Proliferation; D017077:Culture Media, Conditioned / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D059630:Mesenchymal Stem Cells / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D018205:Neoplasms, Adipose Tissue / Q000378:metabolism / Q000473:pathology*; D015398:Signal Transduction; D014183:Transplantation, Heterologous
chemical_list: D015815:Cell Adhesion Molecules; D017077:Culture Media, Conditioned; C512835:POSTN protein, human