Research Papers:

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

Eun-Jung Lim, Yongjoon Suh, Ki-Chun Yoo, Ji-Hyun Lee, In-Gyu Kim, Min-Jung Kim, Jong Hee Chang, Seok-Gu Kang and Su-Jae Lee _

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Oncotarget. 2017; 8:1438-1448. https://doi.org/10.18632/oncotarget.13638

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Eun-Jung Lim1,*, Yongjoon Suh1,*, Ki-Chun Yoo1, Ji-Hyun Lee2, In-Gyu Kim3, Min-Jung Kim4, Jong Hee Chang2, Seok-Gu Kang2, Su-Jae Lee1

1Department of Life Science, Research Institute for Natural Sciences, Hanyang University, Seoul 04763, Republic of Korea

2Department of Neurosurgery, Brain Tumor Center, Severance Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea

3Department of Radiation Biology, Environmental Radiation Research Group, Korea Atomic Energy Research Institute, Daejeon 34057, Republic of Korea

4Laboratory 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: [email protected]

Seok-Gu Kang, email: [email protected]

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


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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