Tumor-associated mesenchymal stem-like cells provide extracellular signaling cue for invasiveness of glioblastoma cells
2017
// Eun-Jung Lim 1, * , Yongjoon Suh 1, * , Ki-Chun Yoo 1 , Ji-Hyun Lee 2 , In-Gyu Kim 3 , Min-Jung Kim 4 , Jong Hee Chang 2 , Seok-Gu Kang 2 , Su-Jae Lee 1 1 Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul 04763, Republic of Korea 2 Department of Neurosurgery, Brain Tumor Center, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea 3 Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, Daejeon 34057, Republic of Korea 4 Laboratory of Radiation Exposure & Therapeutics, National Radiation Emergency Medical Center, Korea Institute of Radiological & Medical Sciences, Seoul 01812, Republic of Korea * These authors have contributed equally to this work Correspondence to: Su-Jae Lee, email: sj0420@hanyang.ac.kr Seok-Gu Kang, email: seokgu9@gmail.com Keywords: extracellular matrix remodeling, mesenchymal stem-like cells, hyaluronic acid, hyaluronic acid synthase-2, C5a Received: October 12, 2016 Accepted: November 11, 2016 Published: November 26, 2016 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.
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