Small cell lung cancer cells express the late stage gBK tumor antigen: a possible immunotarget for the terminal disease

American Journal of Translational Research

Michelle J Hickey¹  Martin R Jadus¹  Carol A Kruse¹  Maria DaCosta-Iyer¹  Rajeev B Tajhya¹  Christine Beeton¹  Erin Hong¹  Neil T Hoa¹  Judy Shon¹  Yi Ouyang¹  Lisheng Ge¹  Kate L Erickson¹  Andrew N Cornforth¹  Nils Lambrecht¹  Anthony P Mai¹  Amir Abolhoda¹ 

关键词: Small cell lung cancer;    BK ion channel;    glioma BK ion channel;    real time PCR;    CTLs;    interferon-γ;   

DOI  :  

学科分类：医学（综合）

来源: e-Century Publishing Corporation

【 摘 要 】

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.

【 授权许可】

Unknown