title: Cellular microenvironment modulates the galvanotaxis of brain tumor initiating cells.
abstract: Galvanotaxis is a complex process that represents the collective outcome of various contributing mechanisms, including asymmetric ion influxes, preferential activation of voltage-gated channels, and electrophoretic redistribution of membrane components. While a large number of studies have focused on various up- and downstream signaling pathways, little is known about how the surrounding microenvironment may interact and contribute to the directional response. Using a customized galvanotaxis chip capable of carrying out experiments in both two- and three-dimensional microenvironments, we show that cell-extracellular matrix (ECM) interactions modulate the galvanotaxis of brain tumor initiating cells (BTICs). Five different BTICs across three different glioblastoma subtypes were examined and shown to all migrate toward the anode in the presence of a direct-current electric field (dcEF) when cultured on a poly-L-ornithine/laminin coated surface, while the fetal-derived neural progenitor cells (fNPCs) migrated toward the cathode. Interestingly, when embedded in a 3D ECM composed of hyaluronic acid and collagen, BTICs exhibited opposite directional response and migrated toward the cathode. Pharmacological inhibition against a panel of key molecules involved in galvanotaxis further revealed the mechanistic differences between 2- and 3D galvanotaxis in BTICs. Both myosin II and phosphoinositide 3-kinase (PI3K) were found to hold strikingly different roles in different microenvironments.
authors.affiliation: Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, Maryland, United States of America.|Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Yu-Ja
authors.initials: YJ
authors.lastname: Huang
authors.affiliation: Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, Maryland, United States of America.|Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Gwendolyn
authors.initials: G
authors.lastname: Hoffmann
authors.affiliation: Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, Maryland, United States of America.|Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Wheeler
authors.affiliation: Department of Neurosurgery and Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Paula
authors.initials: P
authors.lastname: Schiapparelli
authors.affiliation: Department of Neurosurgery and Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Quinones-Hinojosa
authors.affiliation: Institute for Nanobiotechnology, Johns Hopkins University, Baltimore, Maryland, United States of America.|Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, Maryland, United States of America.
authors.forename: Peter
authors.initials: P
authors.lastname: Searson
mesh_terms: D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D060833:Cellular Microenvironment; D004558:Electric Stimulation; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007477:Ions; D024462:Myosin Type II / Q000378:metabolism; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D010455:Peptides / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015398:Signal Transduction; D000071442:Taxis Response
chemical_list: D007477:Ions; D010455:Peptides; C008973:polyornithine; D019869:Phosphatidylinositol 3-Kinases; D024462:Myosin Type II