期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 111, 期 17, 页码 6521-6526出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1404462111
关键词
GBM; surprisal analysis; cancer cell-cell signaling; biological steady state; two-body cell-cell interaction
资金
- National Cancer Institute [5U54 CA119347]
- Jean Perkins Foundation
- Ben and Catherine Ivy Foundation
- European Commission FP7 Future and Emerging Technologies-Open Project BAMBI [618024]
- European Molecular Biology Organization Long-Term Fellowship
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 mu m. 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.
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