정보
Paracrine Function of Human Mesenchymal Stem Cells in Tumor Angi...
Seminar
▶ Subject : Paracrine Function of Human Mesenchymal Stem Cells in Tumor Angiogenesis
▶ Speaker: Prof. Jae Ho Kim(Pusan National University)
▶ Date : 1:00PM/ May. 15(Tue)/2012
▶ Place : Room 376(3F), Postech Biotech Center
*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 pararcine 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 and stimulated tube formation of HUVECs in vitro. To identify proteins involved in the LPA-stimulated pararcine functions of hASCs, we analyzed the LPA CM using liquid-chromatography tandem mass spectrometry-based shotgun proteomics. We identified βig-h3 and periostin, extracellular matrix proteins that are implicated in tumorigenesis and metastasis, as LPA-induced secreted proteins in hASCs. LPA-induced expression of βig-h3 and periostin was abrogated by pretreating hASCs with the LPA receptor1/3 inhibitor Ki16425 or small interfering RNA (siRNA)-mediated silencing of endogenous LPA1. Immunodepletion or siRNA-mediated silencing of βig-h3 and/or periostin abrogated LPA CM-stimulated adhesion and proliferation of A549 cells. Recombinant βig-h3 and periostin proteins stimulated the proliferation and adhesion of A549 human lung adenocarcinoma cells. Furthermore, LPA treatment induced secretion of stromal-derived factor-1 and vascular endothelial growth factor from hASCs. LPA CM-stimulated angiogenesis was abrogated by pharmacological blocking of VEGF receptor. Taken together, these results suggest that hASCs play a key role in tumor growth and angiogenesis by secreting angiogenic factors and extracellular matrix proteins.
☎ Inquiry : Prof. Gho Yong Song(279-2345)
*This Seminar will be given in Korean.