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

Kravchenko-Balasha, Nataly and Wang, Jun and Remacle, Francoise and Levine, R. D. and Heath, James R. (2014) Glioblastoma cellular architectures are predicted through the characterization of two-cell interactions. Proceedings of the National Academy of Sciences of the United States of America, 111 (17). pp. 6521-6526. ISSN 0027-8424. PMCID PMC4035957. http://resolver.caltech.edu/CaltechAUTHORS:20140421-094308358

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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.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1073/pnas.1404462111DOIArticle
http://www.pnas.org/content/111/17/6521PublisherArticle
http://www.pnas.org/content/suppl/2014/04/12/1404462111.DCSupplementalPublisherSupplementary Information
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4035957/PubMed CentralArticle
ORCID:
AuthorORCID
Heath, James R.0000-0001-5356-4385
Additional Information:© 2014 National Academy of Sciences. Contributed by R. D. Levine, March 13, 2014 (sent for review November 21, 2013). We thank Alexander Levitzki and Ayelet Lesman for valuable discussions. Financial support was provided by National Cancer Institute Grant 5U54 CA119347 (to J.R.H.), the Jean Perkins Foundation, the Ben and Catherine Ivy Foundation, and European Commission FP7 Future and Emerging Technologies-Open Project BAMBI 618024 (to F.R. and R.D.L.). N.K.-B. is the recipient of a European Molecular Biology Organization Long-Term Fellowship. F.R. is Director of Fonds National de la Recherche Scientifique, Belgium. N.K.B. and J.W. contributed equally to this work. Author contributions: N.K.-B., R.D.L., and J.R.H. designed research; J.W. designed and performed experimental research; N.K.-B. performed experimental and theoretical research; N.K.-B., R.D.L., and J.R.H. contributed new reagents/analytic tools; N.K.-B., J.W., F.R., R.D.L., and J.R.H. analyzed data; and N.K.-B., F.R., R.D.L., and J.R.H. wrote the paper. The authors declare no conflict of interest. This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1404462111/-/DCSupplemental.
Funders:
Funding AgencyGrant Number
NIH5U54 CA119347
Jean Perkins FoundationUNSPECIFIED
Ben and Catherine Ivy FoundationUNSPECIFIED
European Research Council (ERC)BAMBI 618024
European Molecular Biology Organization (EMBO)UNSPECIFIED
Fonds de la Recherche Scientifique (FNRS)UNSPECIFIED
National Cancer InstituteUNSPECIFIED
Subject Keywords:GBM; surprisal analysis; cancer cell–cell signaling; biological steady state; two-body cell–cell interaction
PubMed Central ID:PMC4035957
Record Number:CaltechAUTHORS:20140421-094308358
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20140421-094308358
Official Citation:Nataly Kravchenko-Balasha, Jun Wang, Francoise Remacle, R. D. Levine, and James R. Heath Glioblastoma cellular architectures are predicted through the characterization of two-cell interactions PNAS 2014 111 (17) 6521-6526; published ahead of print April 14, 2014, doi:10.1073/pnas.1404462111
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:45064
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:21 Apr 2014 22:03
Last Modified:21 Jul 2017 22:02

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