Changes in tumor-antigen expression profile as human small-cell lung cancers progress.
Li-Sheng Ge1, Neil T Hoa1, Nils Lambrecht1
11 Research Service, 2 Pathology and Laboratory Medicine Service, VA Long Beach Healthcare System, Long Beach, CA 90822, USA ; 3 Pathology and Laboratory Medicine, University of California, Irvine, CA 92697, USA ; 4 Surgical Health Care Group, Veterans Affairs Medical Center, Long Beach, CA 90822, USA ; 5 Chao Family Comprehensive Cancer Center, UC, Irvine School of Medicine, University of California, Irvine, Orange, CA 92868, USA.
Small-cell lung cancer (SCLC) patients show increased tumor antigens like glioma big potassium (gBK) ion channel at death. Chemotherapy may induce these antigens, creating more targets for immunotherapy.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- Small-cell lung cancer (SCLC) exhibits differential expression of tumor antigens.
- Glioma big potassium (gBK) ion channel expression is higher at death compared to initial surgical resection in SCLC patients.
Purpose of the Study:
- To investigate if this expression dichotomy is common in other lung tumor antigens.
- To determine if therapeutic intervention influences tumor antigen production, specifically gBK.
Main Methods:
- Quantitative real-time polymerase chain reaction (qRT-PCR) was used to analyze 42 potential tumor-antigen precursor proteins (TAPP) in SCLC samples (surgical and autopsy) and control lungs.
- HTB119 cells were treated with doxorubicin and analyzed for gBK induction via intracellular flow cytometry.
Main Results:
- Twenty-two TAPP mRNAs showed increased expression at autopsy compared to surgical specimens, mirroring gBK.
- B-cyclin and mouse double minute 2 (MDM2) were elevated in both autopsy and surgical SCLC samples above normal controls.
- Doxorubicin treatment strongly induced gBK expression in HTB119 cells.
Conclusions:
- Tumor immunological targets increase as SCLC progresses towards terminal stages.
- Chemotherapy may inadvertently enhance the availability of immunological targets by inducing antigen expression.
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