Journal
ONCOTARGET
Volume 8, Issue 1, Pages 1438-1448Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.13638
Keywords
extracellular matrix remodeling; mesenchymal stem-like cells; hyaluronic acid; hyaluronic acid synthase-2; C5a
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Funding
- National Research Foundation (NRF)
- Ministry of Science, ICT and Future Planning, Korean government [NRF-2012M2B2B1055639, NRF-2015M2A2A7061626]
- National Research Foundation of Korea [2012M2B2B1055639] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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Hyaluronic acid (HA) is abundant in tumor microenvironment and closely associated with invasiveness of glioblastoma (GM) 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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