title: Temozolomide induces the expression of the glioma Big Potassium (gBK) ion channel, while inhibiting fascin-1 expression: possible targets for glioma therapy.
abstract: Temozolomide (TMZ) improves Glioblastoma Multiforme (GBM) patient survival. The invasive behavior of the glioma cells is the cause of GBM relapse. The glioma BK ion channel (gBK) may provide glioma cells with a mechanism to invade surrounding tissue. gBK contains epitopes that cytolytic T lymphocytes (CTLs) can recognize and kill glioma cells. Fascin-1 is an actin crosslinking molecule that supports microvilli; these membrane protrusions provide a physical defense against CTLs. TMZ was investigated to determine its effect on gBK and fascin-1 expression.
  
  
  
  Human glioma cells cultured in TMZ were analyzed for their altered mRNA and gBK protein levels by using quantitative real time PCR, immunostaining and cellular functional assays.
  
  
  
  TMZ slowed glioma cell growth and inhibited their transmigratory properties due to loss of fascin-1. TMZ induced increased gBK and HLA expression and allowed these TMZ-treated cells to become better targets for gBK-specific CTLs.
  
  
  
  Besides its traditional chemotherapeutic effect, TMZ can have four other targeted pathways: 1) slowed glioma cell growth; 2) inhibited glioma cell transmigration; 3) increased HLA-A2 and gBK tumor antigen production; 4) increased CTL-mediated cytolysis of the TMZ treated glioma cells due to the loss of their defensive membrane protrusions supported by fascin-1.
authors.affiliation: a Research Service HCG, Department Veterans Affairs Medical Center , VA Long Beach Healthcare System , Long Beach , CA , USA.
authors.forename: Neil T
authors.initials: NT
authors.lastname: Hoa
authors.affiliation: a Research Service HCG, Department Veterans Affairs Medical Center , VA Long Beach Healthcare System , Long Beach , CA , USA.
authors.forename: Lisheng
authors.initials: L
authors.lastname: Ge
authors.affiliation: a Research Service HCG, Department Veterans Affairs Medical Center , VA Long Beach Healthcare System , Long Beach , CA , USA.|b Laboratory of Pharmaco-Toxicological Analysis; Department of Pharmacy & Biotechnology (FaBiT) , Alma Mater Studiorum - University of Bologna , Bologna , Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Martini
authors.affiliation: a Research Service HCG, Department Veterans Affairs Medical Center , VA Long Beach Healthcare System , Long Beach , CA , USA.
authors.forename: Vincent
authors.initials: V
authors.lastname: Chau
authors.affiliation: a Research Service HCG, Department Veterans Affairs Medical Center , VA Long Beach Healthcare System , Long Beach , CA , USA.
authors.forename: Amrita
authors.initials: A
authors.lastname: Ahluwalia
authors.affiliation: c Department of Neurosurgery, David Geffen School of Medicine , University of California , Los Angeles , CA , USA.
authors.forename: Carol A
authors.initials: CA
authors.lastname: Kruse
authors.affiliation: a Research Service HCG, Department Veterans Affairs Medical Center , VA Long Beach Healthcare System , Long Beach , CA , USA.|d Pathology and Laboratory Medicine Service , Veterans Affairs Medical Center , Long Beach , CA , USA.|e Department of Pathology and Laboratory Medicine , University of California , Orange , CA , USA.|f Chao Comprehensive Cancer Center , University of California , Orange , CA , USA.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Jadus
mesh_terms: D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology; D002352:Carrier Proteins / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy / Q000473:pathology; D005910:Glioma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D006801:Humans; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000235:genetics*; D008840:Microfilament Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D000077204:Temozolomide
chemical_list: D018906:Antineoplastic Agents, Alkylating; D002352:Carrier Proteins; C502658:FSCN1 protein, human; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008840:Microfilament Proteins; D012333:RNA, Messenger; D003606:Dacarbazine; D000077204:Temozolomide
keywords: Cytolytic T lymphocytes; TMZ; fascin-1; glioblastoma multiforme; glioma BK ion channel; microvilli; real time PCR; temozolomide