title: Small cell lung cancer cells express the late stage gBK tumor antigen: a possible immunotarget for the terminal disease.
abstract: Big Potassium (BK) ion channels have several splice variants. One splice variant initially described within human glioma cells is called the glioma BK channel (gBK). Using a gBK-specific antibody, we detected gBK within three human small cell lung cancer (SCLC) lines. Electrophysiology revealed that functional membrane channels were found on the SCLC cells. Prolonged exposure to BK channel activators caused the SCLC cells to swell within 20 minutes and resulted in their death within five hours. Transduction of BK-negative HEK cells with gBK produced functional gBK channels. Quantitative RT-PCR analysis using primers specific for gBK, but not with a lung-specific marker, Sox11, confirmed that advanced, late-stage human SCLC tissues strongly expressed gBK mRNA. Normal human lung tissue and early, lower stage SCLC resected tissues very weakly expressed this transcript. Immunofluorescence using the anti-gBK antibody confirmed that SCLC cells taken at the time of the autopsy intensely displayed this protein. gBK may represent a late-stage marker for SCLC. HLA-A*0201 restricted human CTL were generated in vitro using gBK peptide pulsed dendritic cells. The exposure of SCLC cells to interferon-γ (IFN-γ) increased the expression of HLA; these treated cells were killed by the CTL better than non-IFN-γ treated cells even though the IFN-γ treated SCLC cells displayed diminished gBK protein expression. Prolonged incubation with recombinant IFN-γ slowed the in vitro growth and prevented transmigration of the SCLC cells, suggesting IFN-γ might inhibit tumor growth in vivo. Immunotherapy targeting gBK might impede advancement to the terminal stage of SCLC via two pathways.
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 Molecular Physiology and Biophysics, Baylor College of Medicine Houston, Texas 77030, USA.
authors.forename: Rajeev B
authors.initials: RB
authors.lastname: Tajhya
authors.affiliation: Department of Molecular Physiology and Biophysics, Baylor College of Medicine Houston, Texas 77030, USA.
authors.forename: Christine
authors.initials: C
authors.lastname: Beeton
authors.affiliation: California Stem Cell Inc. 18301 Von Karman Ave, Irvine, CA 92612, USA.
authors.forename: Andrew N
authors.initials: AN
authors.lastname: Cornforth
authors.affiliation: Surgical Health Care Group, Veterans Affairs Medical Center Long Beach, CA 90822, USA.
authors.forename: Amir
authors.initials: A
authors.lastname: Abolhoda
authors.affiliation: 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: Nils
authors.initials: N
authors.lastname: Lambrecht
authors.affiliation: 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: Maria
authors.initials: M
authors.lastname: DaCosta-Iyer
authors.affiliation: 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: Yi
authors.initials: Y
authors.lastname: Ouyang
authors.affiliation: Research Health Care Group, Veterans Affairs Medical Center Long Beach, CA 90822, USA.
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Mai
authors.affiliation: Research Health Care Group, Veterans Affairs Medical Center Long Beach, CA 90822, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: Hong
authors.affiliation: Research Health Care Group, Veterans Affairs Medical Center Long Beach, CA 90822, USA.
authors.forename: Judy
authors.initials: J
authors.lastname: Shon
authors.affiliation: Department of Neurosurgery, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA 90095, USA.
authors.forename: Michelle J
authors.initials: MJ
authors.lastname: Hickey
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: 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 ; Neuro-Oncology Program, Chao Comprehensive Cancer Center, University of California Irvine, Orange, CA 92868, USA.
authors.forename: Martin R
authors.initials: MR
authors.lastname: Jadus
keywords: BK ion channel; CTLs; Small cell lung cancer; glioma BK ion channel; interferon-γ; real time PCR