Endothelial cells promote 3D invasion of GBM by IL-8-dependent induction of cancer stem cell properties

Sci Rep. 2019 Jun 21;9(1):9069. doi: 10.1038/s41598-019-45535-y.


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 types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Brain Neoplasms / pathology*
  • Cell Line, Tumor
  • Coculture Techniques
  • Endothelial Cells / pathology*
  • Glioblastoma / pathology*
  • Humans
  • Interleukin-8 / physiology*
  • Neoplasm Invasiveness*
  • Neoplastic Stem Cells / pathology*


  • CXCL8 protein, human
  • Interleukin-8