title: Fascin-1 knock-down of human glioma cells reduces their microvilli/filopodia while improving their susceptibility to lymphocyte-mediated cytotoxicity.
abstract: Cancer cells derived from Glioblastoma multiforme possess membranous protrusions allowing these cells to infiltrate surrounding tissue, while resisting lymphocyte cytotoxicity. Microvilli and filopodia are supported by actin filaments cross-linked by fascin. Fascin-1 was genetically silenced within human U251 glioma cells; these knock-down glioma cells lost their microvilli/filopodia. The doubling time of these fascin-1 knock-down cells was doubled that of shRNA control U251 cells. Fascin-1 knock-down cells lost their transmigratory ability responding to interleukin-6 or insulin-like growth factor-1. Fascin-1 silenced U251 cells were more easily killed by cytolytic lymphocytes. Fascin-1 knock-down provides unique opportunities to augment glioma immunotherapy by simultaneously targeting several key glioma functions: like cell transmigration, cell division and resisting immune responses.
authors.affiliation: Research Health Care Group, Veterans Affairs Medical Center Long Beach, CA 90822, USA.
authors.forename: Neil T
authors.initials: NT
authors.lastname: Hoa
authors.affiliation: Research Health Care Group, Veterans Affairs Medical Center Long Beach, CA 90822, USA.
authors.forename: Lisheng
authors.initials: L
authors.lastname: Ge
authors.affiliation: Department of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles Los Angeles, CA 90095, USA.
authors.forename: Kate L
authors.initials: KL
authors.lastname: Erickson
authors.affiliation: Department of Neurosurgery, David Geffen School of Medicine, University of California, Los Angeles Los Angeles, CA 90095, USA.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Kruse
authors.affiliation: California Stem Cells, Inc. 18301 Von Karman Avenue Irvine, CA 92612, USA.
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Cornforth
authors.affiliation: Molecular Biology and Biochemistry, University of California, Irvine Irvine, CA 92697, USA.
authors.forename: Yurii
authors.initials: Y
authors.lastname: Kuznetsov
authors.affiliation: Molecular Biology and Biochemistry, University of California, Irvine Irvine, CA 92697, USA.
authors.forename: Alex
authors.initials: A
authors.lastname: McPherson
authors.affiliation: Research Health Care Group, Veterans Affairs Medical Center Long Beach, CA 90822, USA ; Laboratory of Pharmaco-Toxicological Analysis; Department of Pharmacy & Biotechnology (FaBiT), Alma Mater Studiorum - University of Bologna Via Belmeloro 6, 40126 Bologna, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Martini
authors.affiliation: Research Health Care Group, Veterans Affairs Medical Center Long Beach, CA 90822, USA ; Pathology and Laboratory Medicine Service, Veterans Affairs Medical Center Long Beach, CA 90822, USA ; Department of Pathology and Laboratory Medicine, University of California Irvine. Orange, CA 92868, USA.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Jadus
keywords: CTL; Fascin-1; filopodia; glioblastoma; microvilli; shRNA