Glioblastoma cellular architectures are predicted through the characterization of two-cell interactions

Nataly Kravchenko-Balasha, Jun Wang, Francoise Remacle, R. D. Levine, James R. Heath*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

48 Scopus citations

Abstract

To understand how pairwise cellular interactions influence cellular architectures, we measured the levels of functional proteins associated with EGF receptor (EGFR) signaling in pairs of U87EGFR variant III oncogene receptor cells (U87EGFRvIII) at varying cell separations. Using a thermodynamics-derived approach we analyzed the cell-separation dependence of the signaling stability, and identified that the stable steady state of EGFR signaling exists when two U87EGFRvIII cells are separated by 80-100 μm. This distance range was verified as the characteristic intercellular separation within bulk cell cultures. EGFR protein network signaling coordination for the U87EGFRvIII system was lowest at the stable state and most similar to isolated cell signaling. Measurements of cultures of less tumorigenic U87PTEN cells were then used to correctly predict that stable EGFR signaling occurs for those cells at smaller cell-cell separations. The intimate relationship between functional protein levels and cellular architectures explains the scattered nature of U87EGFRvIII cells relative to U87PTEN cells in glioblastoma multiforme tumors.

Original languageAmerican English
Pages (from-to)6521-6526
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume111
Issue number17
DOIs
StatePublished - 29 Apr 2014
Externally publishedYes

Keywords

  • Biological steady state
  • Cancer cell-cell signaling
  • GBM
  • Surprisal analysis
  • Two-body cell-cell interaction

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