Proteomic identification of betaig-h3 as a lysophosphatidic acid-induced secreted protein of human mesenchymal stem cells: paracrine activation of A549 lung adenocarcinoma cells by betaig-h3.

Abstract

Lysophosphatidic acid (LPA) is enriched in the serum and malignant effusion of cancer patients and plays a key role in tumorigenesis and metastasis. LPA-activated mesenchymal stem cells promote tumorigenic potentials of cancer cells through a paracrine mechanism. LPA-conditioned medium (LPA CM) from human adipose tissue-derived mesenchymal stem cells (hASCs) elicited adhesion and proliferation of A549 human lung adenocarcinoma cells. To identify proteins involved in the LPA-stimulated paracrine functions of hASCs, we analyzed the LPA CM using liquid-chromatography tandem mass spectrometry-based shotgun proteomics. We identified βig-h3, an extracellular matrix protein that is implicated in tumorigenesis and metastasis, as an LPA-induced secreted protein in hASCs. LPA-induced βig-h3 expression was abrogated by pretreating hASCs with the LPA receptor(1/3) inhibitor Ki16425 or small interfering RNA-mediated silencing of endogenous LPA(1). LPA-induced βig-h3 expression was blocked by treating the cells with the Rho kinase inhibitor Y27632, implying that LPA-induced βig-h3 expression is mediated by the LPA(1)- Rho kinase pathway. Immunodepletion or siRNA-mediated silencing of βig-h3 abrogated LPA CM-stimulated adhesion and proliferation of A549 cells, whereas retroviral overexpression of βig-h3 in hASCs potentiated it. Furthermore, recombinant βig-h3 protein stimulated the proliferation and adhesion of A549 human lung adenocarcinoma cells. These results suggest that hASC-derived βig-h3 plays a key role in tumorigenesis by stimulating the adhesion and proliferation of cancer cells and it can be applicable as a biomarker and therapeutic target for lung cancer.

• Authors: Sang Hun Shin, Jaeyoon Kim, Soon Chul Heo, Yang Woo Kwon, Young Mi Kim, In-San Kim, Taehoon G Lee, Jae Ho Kim
• Journal: Molecular & cellular proteomics : MCP (Mol Cell Proteomics) Vol. 11 Issue 2 Pg. M111.012385 (Feb 2012) ISSN: 1535-9484 [Electronic] United States
• PMID: 22159598 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Culture Media, Conditioned
• Extracellular Matrix Proteins
• Lysophospholipids
• Proteome
• Receptors, Lysophosphatidic Acid
• Transforming Growth Factor beta
• betaIG-H3 protein
• rho-Associated Kinases
• lysophosphatidic acid

Topics

• Adenocarcinoma (metabolism, pathology)
• Adipose Tissue (cytology, metabolism)
• Blotting, Western
• Cell Adhesion
• Cell Line, Tumor
• Cell Proliferation
• Chromatography, Liquid
• Culture Media, Conditioned (pharmacology)
• Extracellular Matrix Proteins (metabolism)
• Humans
• Lung Neoplasms (metabolism, pathology)
• Lysophospholipids (pharmacology)
• Mesenchymal Stem Cells (cytology, metabolism)
• Paracrine Communication
• Proteome (analysis)
• Proteomics
• Receptors, Lysophosphatidic Acid (metabolism)
• Tandem Mass Spectrometry
• Transforming Growth Factor beta (metabolism)
• Tumor Cells, Cultured
• rho-Associated Kinases (metabolism)