Endothelial cells promote 3D invasion of GBM by IL-8-dependent induction of cancer stem cell properties. Academic Article uri icon

Overview

abstract

  • Rapid growth and perivascular invasion are hallmarks of glioblastoma (GBM) that have been attributed to the presence of cancer stem-like cells (CSCs) and their association with the perivascular niche. However, the mechanisms by which the perivascular niche regulates GBM invasion and CSCs remain poorly understood due in part to a lack of relevant model systems. To simulate perivascular niche conditions and analyze consequential changes of GBM growth and invasion, patient-derived GBM spheroids were co-cultured with brain endothelial cells (ECs) in microfabricated collagen gels. Integrating these systems with 3D imaging and biochemical assays revealed that ECs increase GBM invasiveness and growth through interleukin-8 (IL-8)-mediated enrichment of CSCs. Blockade of IL-8 inhibited these effects in GBM-EC co-cultures, while IL-8 supplementation increased CSC-mediated growth and invasion in GBM-monocultures. Experiments in mice confirmed that ECs and IL-8 stimulate intracranial tumor growth and invasion in vivo. Collectively, perivascular niche conditions promote GBM growth and invasion by increasing CSC frequency, and IL-8 may be explored clinically to inhibit these interactions.

publication date

  • June 21, 2019

Research

keywords

  • Brain Neoplasms
  • Endothelial Cells
  • Glioblastoma
  • Interleukin-8
  • Neoplasm Invasiveness
  • Neoplastic Stem Cells

Identity

PubMed Central ID

  • PMC6588602

Scopus Document Identifier

  • 85067832533

Digital Object Identifier (DOI)

  • 10.1089/ten.tea.2009.0670

PubMed ID

  • 31227783

Additional Document Info

volume

  • 9

issue

  • 1