title: Glioblastoma cellular architectures are predicted through the characterization of two-cell interactions.
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.
authors.affiliation: NanoSystems Biology Cancer Center, Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125.
authors.forename: Nataly
authors.initials: N
authors.lastname: Kravchenko-Balasha
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Francoise
authors.initials: F
authors.lastname: Remacle
authors.forename: R D
authors.initials: RD
authors.lastname: Levine
authors.forename: James R
authors.initials: JR
authors.lastname: Heath
mesh_terms: D001932:Brain Neoplasms / Q000473:pathology*; D002450:Cell Communication; D045744:Cell Line, Tumor; D066246:ErbB Receptors / Q000378:metabolism; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D008954:Models, Biological; D015203:Reproducibility of Results; D015398:Signal Transduction; D059010:Single-Cell Analysis
chemical_list: D066246:ErbB Receptors
keywords: GBM; biological steady state; cancer cell–cell signaling; surprisal analysis; two-body cell–cell interaction
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