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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Lee, Min Ki Shin, Sang Hun Kim, Jae Ho Kwon, Yang Woo Yoon, Man-soo Kim, Young Mi Lee, Chang Hun Lee, Kook One Kim, Yeong Dae Heo, Soon Chul |
| Description | Author Affiliation: Heo SC ( Medical Research Center for Ischemic Tissue Regeneration, Pusan National University, Yangsan, Republic of Korea.) |
| 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. |
| ISSN | 00063002 |
| Journal | Biochimica et Biophysica Acta (BBA) - Reviews on Cancer |
| Issue Number | 12 |
| Volume Number | 1813 |
| Language | English |
| Publisher | Elsevier |
| Publisher Date | 2011-12-01 |
| Publisher Place | Netherlands |
| Access Restriction | Open |
| Subject Keyword | Adenocarcinoma Pathology Adipose Tissue Cell Adhesion Molecules Metabolism Lung Neoplasms Mesenchymal Stromal Cells Neoplasms, Adipose Tissue Animals Blotting, Western Cell Adhesion Genetics Cell Proliferation Culture Media, Conditioned Pharmacology Mice Mice, Inbred BALB C Mice, Nude Signal Transduction Transplantation, Heterologous Research Support, Non-U.S. Gov't Biochemistry |
| Content Type | Text |
| Resource Type | Article |
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