[en] 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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Kravchenko-Balasha, Nataly
Wang, Jun
Remacle, Françoise ; Université de Liège > Département de chimie (sciences) > Laboratoire de chimie physique théorique
Levine, Raphaël David
Heath, James R.
Language :
English
Title :
Glioblastoma cellular architectures are predicted through the characterization of two-cell interactions
Publication date :
2014
Journal title :
Proceedings of the National Academy of Sciences of the United States of America
ISSN :
0027-8424
eISSN :
1091-6490
Publisher :
National Academy of Sciences, Washington, United States - District of Columbia
Inda MM, et al. (2010) Tumor heterogeneity is an active process maintained by a mutant EGFR-induced cytokine circuit in glioblastoma. Genes Dev 24(16): 1731-1745.
Lal A, et al. (2002) Mutant epidermal growth factor receptor up-regulates molecular effectors of tumor invasion. Cancer Res 62(12):3335-3339.
Bonavia R, Inda MM, Cavenee WK, Furnari FB (2011) Heterogeneity maintenance in glioblastoma: A social network. Cancer Res 71(12):4055-4060.
Nishikawa R, et al. (2004) Immunohistochemical analysis of the mutant epidermal growth factor, deltaEGFR, in glioblastoma. Brain Tumor Pathol 21(2):53-56.
da Fonseca AC, Badie B (2013) Microglia and macrophages in malignant gliomas: Recent discoveries and implications for promising therapies. Clin Dev Immunol 2013:264124.
Huang J, et al. (2007) Transactivation of the epidermal growth factor receptor by formylpeptide receptor exacerbates the malignant behavior of human glioblastoma cells. Cancer Res 67(12):5906-5913.
Mukherjee J, et al. (2009) Loss of collapsin response mediator Protein1, as detected by iTRAQ analysis, promotes invasion of human gliomas expressing mutant EGFRvIII. Cancer Res 69(22):8545-8554.
Sciaccaluga M, et al. (2010) CXCL12-induced glioblastoma cell migration requires intermediate conductance Ca2+-activated K+ channel activity. Am J Physiol Cell Physiol 299(1):C175-C184.
Laidler K (1996) A glossary of terms used in chemical kinetics, including reaction dynamics (IUPAC Recommendations 1996). Pure Appl Chem 68(1):149-192.
Levine RD, Bernstein RB (1974) Energy disposal and energy consumption in elementary chemical reactions. Information theoretic approach. Acc Chem Res 7(12): 393-400.
Remacle F, Kravchenko-Balasha N, Levitzki A, Levine RD (2010) Information-theoretic analysis of phenotype changes in early stages of carcinogenesis. Proc Natl Acad Sci USA 107(22):10324-10329.
Wang J, et al. (2012) Quantitating cell-cell interaction functions with applications to glioblastoma multiforme cancer cells. Nano Lett 12(12):6101-6106.
Shi Q, et al. (2012) Single-cell proteomic chip for profiling intracellular signaling pathways in single tumor cells. Proc Natl Acad Sci USA 109(2):419-424.
Kravchenko-Balasha N, et al. (2012) On a fundamental structure of gene networks in living cells. Proc Natl Acad Sci USA 109(12):4702-4707.
Kravchenko-Balasha N, et al. (2011) Convergence of logic of cellular regulation in different premalignant cells by an information theoretic approach. BMC Syst Biol 5:42.
Xie Q, et al. (2008) A highly invasive human glioblastoma pre-clinical model for testing therapeutics. J Transl Med 6:77.
Sun S, et al. (2011) Knockdown of CypA inhibits interleukin-8 (IL-8) and IL-8-mediated proliferation and tumor growth of glioblastoma cells through down-regulated NF-κB. J Neurooncol 101(1):1-14.
McQuarrie DA (2000) Statistical Mechanics (University Science Books, Sausalito, CA).
Parsa AT, et al. (2007) Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma. Nat Med 13(1):84-88.
Wang MY, et al. (2006) Mammalian target of rapamycin inhibition promotes response to epidermal growth factor receptor kinase inhibitors in PTEN-deficient and PTENintact glioblastoma cells. Cancer Res 66(16):7864-7869.
Hatanpaa KJ, Burma S, Zhao D, Habib AA (2010) Epidermal growth factor receptor in glioma: Signal transduction, neuropathology, imaging, and radioresistance. Neoplasia 12(9):675-684.