Multidimensional hydrogel models reveal endothelial network angiocrine signals increase glioblastoma cell number, invasion, and temozolomide resistance

Mai T. Ngo, Elijah Karvelis, Brendan A.C. Harley

Research output: Contribution to journalArticlepeer-review

Abstract

Glioblastoma (GBM) is the most common primary malignant brain tumor. The tissue microenvironment adjacent to vasculature, termed the perivascular niche, has been implicated in promoting biological processes involved in glioblastoma progression such as invasion, proliferation, and therapeutic resistance. However, the exact nature of the cues that support tumor cell aggression in this niche is largely unknown. Soluble angiocrine factors secreted by tumor-associated vasculature have been shown to support such behaviors in other cancer types. Here, we exploit macroscopic and microfluidic gelatin hydrogel platforms to profile angiocrine factors secreted by self-assembled endothelial networks and evaluate their relevance to glioblastoma biology. Aggregate angiocrine factors support increases in U87-MG cell number, migration, and therapeutic resistance to temozolomide. We also identify a novel role for TIMP1 in facilitating glioblastoma tumor cell migration. Overall, this work highlights the use of multidimensional hydrogel models to evaluate the role of angiocrine signals in glioblastoma progression.

Original languageEnglish (US)
Pages (from-to)139-149
Number of pages11
JournalIntegrative biology : quantitative biosciences from nano to macro
Volume12
Issue number6
DOIs
StatePublished - Jun 19 2020

Keywords

  • TIMP1
  • angiocrine
  • glioblastoma
  • hydrogel
  • invasion
  • microfluidic
  • temozolomide
  • three-dimensional
  • vascular

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry

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