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

Sang Hun Shin, Jaeyoon Kim, Soon Chul Heo, Yang Woo Kwon, Young Mi Kim, In-San Kim, Taehoon G. Lee, Jae Ho Kim

Research output: Contribution to journalArticle

18 Citations (Scopus)

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.

Original languageEnglish
JournalMolecular and Cellular Proteomics
Volume11
Issue number2
DOIs
Publication statusPublished - 2012 Feb 1
Externally publishedYes

Fingerprint

Stem cells
Mesenchymal Stromal Cells
Proteomics
Chemical activation
Adipose Tissue
Proteins
Tissue
rho-Associated Kinases
Carcinogenesis
Adhesion
Small Interfering RNA
Adenocarcinoma of lung
lysophosphatidic acid
Lysophosphatidic Acid Receptors
Cells
Cell Proliferation
Neoplasm Metastasis
Neoplasms
Extracellular Matrix Proteins
Cell adhesion

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Molecular Biology

Cite this

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. / Shin, Sang Hun; Kim, Jaeyoon; Heo, Soon Chul; Kwon, Yang Woo; Kim, Young Mi; Kim, In-San; Lee, Taehoon G.; Kim, Jae Ho.

In: Molecular and Cellular Proteomics, Vol. 11, No. 2, 01.02.2012.

Research output: Contribution to journalArticle

@article{cac5919602664f83a44f12f2d1bd2fdd,
title = "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.",
author = "Shin, {Sang Hun} and Jaeyoon Kim and Heo, {Soon Chul} and Kwon, {Yang Woo} and Kim, {Young Mi} and In-San Kim and Lee, {Taehoon G.} and Kim, {Jae Ho}",
year = "2012",
month = "2",
day = "1",
doi = "10.1074/mcp.M111.012385",
language = "English",
volume = "11",
journal = "Molecular and Cellular Proteomics",
issn = "1535-9476",
publisher = "American Society for Biochemistry and Molecular Biology Inc.",
number = "2",

}

TY - JOUR

T1 - Proteomic identification of betaig-h3 as a lysophosphatidic acid-induced secreted protein of human mesenchymal stem cells

T2 - Paracrine activation of A549 lung adenocarcinoma cells by betaig-h3

AU - Shin, Sang Hun

AU - Kim, Jaeyoon

AU - Heo, Soon Chul

AU - Kwon, Yang Woo

AU - Kim, Young Mi

AU - Kim, In-San

AU - Lee, Taehoon G.

AU - Kim, Jae Ho

PY - 2012/2/1

Y1 - 2012/2/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84863079772&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84863079772&partnerID=8YFLogxK

U2 - 10.1074/mcp.M111.012385

DO - 10.1074/mcp.M111.012385

M3 - Article

VL - 11

JO - Molecular and Cellular Proteomics

JF - Molecular and Cellular Proteomics

SN - 1535-9476

IS - 2

ER -