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01-04-2019 | Glioblastoma | Original Article

Targeting Hyaluronan Interactions for Glioblastoma Stem Cell Therapy

Authors: Joline S. Hartheimer, Seungjo Park, Shreyas S. Rao, Yonghyun Kim

Published in: Cancer Microenvironment | Issue 1/2019

Abstract

Even with rigorous treatments, glioblastoma multiforme (GBM) has an abysmal median survival rate, greatly due to the drug-resistant glioblastoma stem cell (GSC) population. GSCs are known to remodel their microenvironment, but the precise role of extracellular matrix components hyaluronic acid (HA) and hyaluronidases (HAases) on the GSC population is still largely unknown. Our objective was to determine how HAase can sensitize GSCs to chemotherapy drugs by disrupting the HA-CD44 signaling. GBM cell line U87-MG and patient-derived D456 cells were grown in GSC-enriching media and treated with HA or HAase. Expressions of GSC markers, HA-related genes, and drug resistance genes were measured via flow cytometry, confocal microscopy, and qRT-PCR. Proliferation after combined HAase and temozolomide (TMZ) treatment was measured via WST-8. HA supplementation promoted the expression of GSC markers and CD44 in GBM cells cultured in serum-free media. Conversely, HAase addition inhibited GSC gene expression while promoting CD44 expression. Finally, HAase sensitized GBM cells to TMZ. We propose a combined treatment of HAase and chemotherapy drugs by disrupting the stemness-promoting HA to target GSCs. This combination therapy shows promise even when temozolomide treatment alone causes resistance.

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Title: Targeting Hyaluronan Interactions for Glioblastoma Stem Cell Therapy
Authors: Joline S. Hartheimer
Seungjo Park
Shreyas S. Rao
Yonghyun Kim
Publication date: 01-04-2019
Publisher: Springer Netherlands
Keywords: Glioblastoma
Glioblastoma
Glioblastoma
Published in: Cancer Microenvironment / Issue 1/2019
Print ISSN: 1875-2292
Electronic ISSN: 1875-2284
DOI: https://doi.org/10.1007/s12307-019-00224-2

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