title: Tumor-associated mesenchymal stem-like cells provide extracellular signaling cue for invasiveness of glioblastoma 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.
authors.affiliation: Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul 04763, Republic of Korea.
authors.forename: Eun-Jung
authors.initials: EJ
authors.lastname: Lim
authors.affiliation: Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul 04763, Republic of Korea.
authors.forename: Yongjoon
authors.initials: Y
authors.lastname: Suh
authors.affiliation: Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul 04763, Republic of Korea.
authors.forename: Ki-Chun
authors.initials: KC
authors.lastname: Yoo
authors.affiliation: Department of Neurosurgery, Brain Tumor Center, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
authors.forename: Ji-Hyun
authors.initials: JH
authors.lastname: Lee
authors.affiliation: Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, Daejeon 34057, Republic of Korea.
authors.forename: In-Gyu
authors.initials: IG
authors.lastname: Kim
authors.affiliation: Laboratory of Radiation Exposure & Therapeutics, National Radiation Emergency Medical Center, Korea Institute of Radiological & Medical Sciences, Seoul 01812, Republic of Korea.
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Kim
authors.affiliation: Department of Neurosurgery, Brain Tumor Center, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
authors.forename: Jong Hee
authors.initials: JH
authors.lastname: Chang
authors.affiliation: Department of Neurosurgery, Brain Tumor Center, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
authors.forename: Seok-Gu
authors.initials: SG
authors.lastname: Kang
authors.affiliation: Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul 04763, Republic of Korea.
authors.forename: Su-Jae
authors.initials: SJ
authors.lastname: Lee
mesh_terms: D000368:Aged; D000818:Animals; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D064593:Heterografts; D006801:Humans; D018960:Hyaluronan Receptors / Q000378:metabolism; D006820:Hyaluronic Acid / Q000494:pharmacology; D008024:Ligands; D008297:Male; D059630:Mesenchymal Stem Cells / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness; D015398:Signal Transduction
chemical_list: D016326:Extracellular Matrix Proteins; D018960:Hyaluronan Receptors; D008024:Ligands; C098946:hyaluronan-mediated motility receptor; D006820:Hyaluronic Acid
keywords: C5a; extracellular matrix remodeling; hyaluronic acid; hyaluronic acid synthase-2; mesenchymal stem-like cells