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Tumor-associated mesenchymal stem-like cells provide extracellular signaling cue for invasiveness of glioblastoma cells

Authors
 Eun-Jung Lim  ;  Yongjoon Suh  ;  Ki-Chun Yoo  ;  Ji-Hyun Lee  ;  In-Gyu Kim  ;  Min-Jung Kim  ;  Jong Hee Chang  ;  Seok-Gu Kang  ;  Su-Jae Lee 
Citation
 Oncotarget, Vol.8(1) : 1438-1448, 2017 
Journal Title
 Oncotarget 
Issue Date
2017
MeSH
Aged ; Animals ; Brain Neoplasms/metabolism* ; Brain Neoplasms/pathology ; Extracellular Matrix Proteins/metabolism ; Female ; Glioblastoma/metabolism* ; Glioblastoma/pathology ; Heterografts ; Humans ; Hyaluronan Receptors/metabolism ; Hyaluronic Acid/pharmacology ; Ligands ; Male ; Mesenchymal Stromal Cells/metabolism* ; Mesenchymal Stromal Cells/pathology ; Mice ; Mice, Nude ; Neoplasm Invasiveness ; Signal Transduction
Keywords
C5a ; extracellular matrix remodeling ; hyaluronic acid ; hyaluronic acid synthase-2 ; mesenchymal stem-like cells
Abstract
Hyaluronic acid (HA) is abundant in tumor microenvironment and closely associated with invasiveness of glioblastoma (GBM) cells. However, the cellular mechanism underlying HA-rich microenvironment in GBM remains unexplored. Here, we show that tumor-associated mesenchymal stem-like cells (tMSLCs) contribute to abundance of hyaluronic acid (HA) in tumor microenvironment through HA synthase-2 (HAS2) induction, and thereby enhances invasiveness of GBM cells. In an autocrine manner, C5a secreted by tMSLCs activated ERK MAPK for HAS2 induction in tMSLCs. Importantly, HA acted as a signaling ligand of its cognate receptor RHAMM for intracellular signaling activation underlying invasiveness of GBM cells. Taken together, our study suggests that tMSLCs contribute to HA-rich proinvasive ECM microenvironment in GBM.
Files in This Item:
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DOI
10.18632/oncotarget.13638
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Neurosurgery (신경외과학교실) > 1. Journal Papers
Yonsei Authors
Kang, Seok Gu(강석구) ORCID logo https://orcid.org/0000-0001-5676-2037
Lee, Ji Hyun(이지현) ORCID logo https://orcid.org/0000-0002-9223-9478
Chang, Jong Hee(장종희)
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URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/154084
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