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Glioblastoma Spheroid Invasion through Soft, Brain-Like Matrices Depends on Hyaluronic Acid-CD44 Interactions.
Safarians, Gevick; Sohrabi, Alireza; Solomon, Itay; Xiao, Weikun; Bastola, Soniya; Rajput, Bushra W; Epperson, Mary; Rosenzweig, Isabella; Tamura, Kelly; Singer, Breahna; Huang, Joyce; Harrison, Mollie J; Sanazzaro, Talia; Condro, Michael C; Kornblum, Harley I; Seidlits, Stephanie K.
Affiliation
  • Safarians G; Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, 90095, USA.
  • Sohrabi A; Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, 90095, USA.
  • Solomon I; Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, 78712, USA.
  • Xiao W; Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, 90095, USA.
  • Bastola S; Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, 90095, USA.
  • Rajput BW; Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, 90095, USA.
  • Epperson M; Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, 90024, USA.
  • Rosenzweig I; Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, 90095, USA.
  • Tamura K; Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, 90095, USA.
  • Singer B; Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, 90095, USA.
  • Huang J; Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, 90095, USA.
  • Harrison MJ; Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, 90095, USA.
  • Sanazzaro T; Department of Bioengineering, University of California Los Angeles, Los Angeles, CA, 90095, USA.
  • Condro MC; Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, 78712, USA.
  • Kornblum HI; Department of Biomedical Engineering, The University of Texas at Austin, Austin, TX, 78712, USA.
  • Seidlits SK; Semel Institute for Neuroscience and Human Behavior, University of California Los Angeles, Los Angeles, CA, 90024, USA.
Adv Healthc Mater ; 12(14): e2203143, 2023 06.
Article in En | MEDLINE | ID: mdl-36694362
ABSTRACT
Increased secretion of hyaluronic acid (HA), a glycosaminoglycan abundant in the brain extracellular matrix (ECM), correlates with worse clinical outcomes for glioblastoma (GBM) patients. GBM cells aggressively invade the brain parenchyma while encountering spatiotemporal changes in their local ECM, including HA concentration. To investigate how varying HA concentrations affect GBM invasion, patient-derived GBM cells are cultured within a soft, 3D matrix in which HA concentration is precisely varied and cell migration observed. Data demonstrate that HA concentration can determine the invasive activity of patient-derived GBM cells in a biphasic and highly sensitive manner, where the absolute concentration of HA at which cell migration peaked is specific to each patient-derived line. Furthermore, evidence that this response relies on phosphorylated ezrin, which interacts with the intracellular domain of HA-engaged CD44 to effectively link the actin cytoskeleton to the local ECM is provided. Overall, this study highlights CD44-HA binding as a major mediator of GBM cell migration that acts independently of integrins and focal adhesion complexes and suggests that targeting HA-CD44-ezrin interactions represents a promising therapeutic strategy to prevent tumor cell invasion in the brain.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Glioblastoma Limits: Humans Language: En Journal: Adv Healthc Mater Year: 2023 Document type: Article Affiliation country: Estados Unidos
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Glioblastoma Limits: Humans Language: En Journal: Adv Healthc Mater Year: 2023 Document type: Article Affiliation country: Estados Unidos