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Electrotaxis of Glioblastoma and Medulloblastoma Spheroidal Aggregates.
Sci Rep 2019; 9(1):5309SR

Abstract

Treatment of neuroepithelial cancers remains a daunting clinical challenge, particularly due to an inability to address rampant invasion deep into eloquent regions of the brain. Given the lack of access, and the dispersed nature of brain tumor cells, we explore the possibility of electric fields inducing directed tumor cell migration. In this study we investigate the properties of populations of brain cancer undergoing electrotaxis, a phenomenon whereby cells are directed to migrate under control of an electrical field. We investigate two cell lines for glioblastoma and medulloblastoma (U87mg & DAOY, respectively), plated as spheroidal aggregates in Matrigel-filled electrotaxis channels, and report opposing electrotactic responses. To further understand electrotactic migration of tumor cells, we performed RNA-sequencing for pathway discovery to identify signaling that is differentially affected by the exposure of direct-current electrical fields. Further, using selective pharmacological inhibition assays, focused on the PI3K/mTOR/AKT signaling axis, we validate whether there is a causal relationship to electrotaxis and these mechanisms of action. We find that U87 mg electrotaxis is abolished under pharmacological inhibition of PI3Kγ, mTOR, AKT and ErbB2 signaling, whereas DAOY cell electrotaxis was not attenuated by these or other pathways evaluated.

Authors+Show Affiliations

Department of Biomedical Engineering, Pratt School of Engineering, Duke University, 101 Science Drive, Durham, NC, 27705, USA. j.lyon@duke.edu. Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology & Emory School of Medicine, UA Whitaker Building, 313 Ferst Drive, Atlanta, GA, 30332, USA. j.lyon@duke.edu.Department of Biomedical Engineering, Pratt School of Engineering, Duke University, 101 Science Drive, Durham, NC, 27705, USA.Department of Biomedical Engineering, Pratt School of Engineering, Duke University, 101 Science Drive, Durham, NC, 27705, USA.Department of Biomedical Engineering, Pratt School of Engineering, Duke University, 101 Science Drive, Durham, NC, 27705, USA. ravi@duke.edu.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

30926929

Citation

Lyon, Johnathan G., et al. "Electrotaxis of Glioblastoma and Medulloblastoma Spheroidal Aggregates." Scientific Reports, vol. 9, no. 1, 2019, p. 5309.
Lyon JG, Carroll SL, Mokarram N, et al. Electrotaxis of Glioblastoma and Medulloblastoma Spheroidal Aggregates. Sci Rep. 2019;9(1):5309.
Lyon, J. G., Carroll, S. L., Mokarram, N., & Bellamkonda, R. V. (2019). Electrotaxis of Glioblastoma and Medulloblastoma Spheroidal Aggregates. Scientific Reports, 9(1), p. 5309. doi:10.1038/s41598-019-41505-6.
Lyon JG, et al. Electrotaxis of Glioblastoma and Medulloblastoma Spheroidal Aggregates. Sci Rep. 2019 Mar 29;9(1):5309. PubMed PMID: 30926929.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Electrotaxis of Glioblastoma and Medulloblastoma Spheroidal Aggregates. AU - Lyon,Johnathan G, AU - Carroll,Sheridan L, AU - Mokarram,Nassir, AU - Bellamkonda,Ravi V, Y1 - 2019/03/29/ PY - 2018/07/13/received PY - 2019/02/26/accepted PY - 2019/3/31/entrez PY - 2019/3/31/pubmed PY - 2019/3/31/medline SP - 5309 EP - 5309 JF - Scientific reports JO - Sci Rep VL - 9 IS - 1 N2 - Treatment of neuroepithelial cancers remains a daunting clinical challenge, particularly due to an inability to address rampant invasion deep into eloquent regions of the brain. Given the lack of access, and the dispersed nature of brain tumor cells, we explore the possibility of electric fields inducing directed tumor cell migration. In this study we investigate the properties of populations of brain cancer undergoing electrotaxis, a phenomenon whereby cells are directed to migrate under control of an electrical field. We investigate two cell lines for glioblastoma and medulloblastoma (U87mg & DAOY, respectively), plated as spheroidal aggregates in Matrigel-filled electrotaxis channels, and report opposing electrotactic responses. To further understand electrotactic migration of tumor cells, we performed RNA-sequencing for pathway discovery to identify signaling that is differentially affected by the exposure of direct-current electrical fields. Further, using selective pharmacological inhibition assays, focused on the PI3K/mTOR/AKT signaling axis, we validate whether there is a causal relationship to electrotaxis and these mechanisms of action. We find that U87 mg electrotaxis is abolished under pharmacological inhibition of PI3Kγ, mTOR, AKT and ErbB2 signaling, whereas DAOY cell electrotaxis was not attenuated by these or other pathways evaluated. SN - 2045-2322 UR - https://www.unboundmedicine.com/medline/citation/30926929/Electrotaxis_of_Glioblastoma_and_Medulloblastoma_Spheroidal_Aggregates L2 - http://dx.doi.org/10.1038/s41598-019-41505-6 DB - PRIME DP - Unbound Medicine ER -