@article{7ee65351ecd14020b12c7ad579a2ecd8,
title = "Targeting Glioblastoma Tumor Hyaluronan to Enhance Therapeutic Interventions that Regulate Metabolic Cell Properties",
abstract = "Despite extensive advances in cancer research, glioblastoma (GBM) still remains a very locally invasive and thus challenging tumor to treat, with a poor median survival. Tumor cells remodel their microenvironment and utilize extracellular matrix to promote invasion and therapeutic resistance. It is aimed here to determine how GBM cells exploit hyaluronan (HA) to maintain proliferation using ligand-receptor dependent and ligand-receptor independent signaling. Tissue engineering approaches are used to recreate the 3D tumor microenvironment in vitro, then analyze shifts in metabolism, hyaluronan secretion, HA molecular weight distribution, as well as hyaluronan synthetic enzymes (HAS) and hyaluronidases (HYAL) activity in an array of patient-derived xenograft GBM cells. It is revealed that endogenous HA plays a role in mitochondrial respiration and cell proliferation in a tumor subtype-dependent manner. A tumor-specific combination treatment of HYAL and HAS inhibitors is proposed to disrupt the HA stabilizing role in GBM cells. Taken together, these data shed light on the dual metabolic and ligand – dependent signaling roles of hyaluronan in glioblastoma.",
keywords = "brain cancer, engineered disease models, glioblastoma, hyaluronan metabolism, hydrogel, tumor microenvironment",
author = "Neves, {Edward R.} and Achal Anand and Joseph Mueller and Remy, {Roddel A.} and Hui Xu and Selting, {Kim A.} and Sarkaria, {Jann N.} and Harley, {Brendan A.C.} and Sara Pedron-Haba",
note = "The authors would like to acknowledge the following institutes for access to their facilities and services: the Roy J. Carver Biotechnology Center at UIUC, the School of Chemical Sciences Microanalysis Laboratory, the Tumor Engineering and Phenotyping Core at the Cancer Center at Illinois, the Carle R Woese Institute for Genomic Biology and the Materials Research Laboratory. Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number R01 CA256481 (B.A.C.H.) as well as the Bahl Family Research Fund from the Cancer Center at Illinois (B.A.C.H.). The interpretations and conclusions presented are those of the authors and are not necessarily endorsed by the National Institutes of Health. The authors thank the Cancer Center at Illinois at the University of Illinois Urbana-Champaign for supporting this work. This project is supported by funding made available through the Cancer Center at Illinois Pilot Grant Program. Some figures are created with BioRender.com. The authors would like to acknowledge the following institutes for access to their facilities and services: the Roy J. Carver Biotechnology Center at UIUC, the School of Chemical Sciences Microanalysis Laboratory, the Tumor Engineering and Phenotyping Core at the Cancer Center at Illinois, the Carle R Woese Institute for Genomic Biology and the Materials Research Laboratory. Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number R01 CA256481 (B.A.C.H.) as well as the Bahl Family Research Fund from the Cancer Center at Illinois (B.A.C.H.). The interpretations and conclusions presented are those of the authors and are not necessarily endorsed by the National Institutes of Health. The authors thank the Cancer Center at Illinois at the University of Illinois Urbana\u2010Champaign for supporting this work. This project is supported by funding made available through the Cancer Center at Illinois Pilot Grant Program. Some figures are created with BioRender.com.",
year = "2024",
month = oct,
doi = "10.1002/adtp.202400041",
language = "English (US)",
volume = "7",
journal = "Advanced Therapeutics",
issn = "2366-3987",
publisher = "Wiley-Blackwell",
number = "10",
}