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Changes in tumor-antigen expression profile as human small-cell lung cancers progress.

Ge LS, Hoa NT, Lambrecht N, Dacosta-Iyer M, Ouyang Y, Abolhoda A, Jadus MR - Cancer Biol Med (2015)

Bottom Line: Our group has previously observed that in patients with small-cell lung cancers (SCLCs), the expression of a tumor antigen, glioma big potassium (gBK) ion channel, is higher at the time of death than when the cancer is first treated by surgical resection.When HTB119 cells were incubated with doxorubicin, gBK was strongly induced, as confirmed by intracellular flow cytometry with a gBK-specific antibody.Our findings suggested that more immunological targets became available as the tumor responded to chemotherapy and proceeded toward its terminal stages.

View Article: PubMed Central - PubMed

Affiliation: 1 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.

ABSTRACT

Objective: Our group has previously observed that in patients with small-cell lung cancers (SCLCs), the expression of a tumor antigen, glioma big potassium (gBK) ion channel, is higher at the time of death than when the cancer is first treated by surgical resection. This study aimed to determine whether this dichotomy was common in other potential lung tumor antigens by examining the same patient samples using our more extensive profile analysis of tumor-antigen precursor protein (TAPP). We then tested the hypothesis that therapeutic intervention may inadvertently cause this increased gBK production.

Methods: SCLC samples (eight surgical resections and three autopsy samples) and three control lungs were examined by quantitative real-time polymerase chain reaction for 42 potential TAPPs that represent potential T-cell-mediated immunological targets.

Results: Twenty-two TAPP mRNAs displayed the same profile as gBK, i.e., more mRNAs were expressed at autopsy than in their surgical counterparts. B-cyclin and mouse double minute 2, human homolog of P53-binding protein were elevated in both autopsy and surgical specimens above the normal-lung controls. When HTB119 cells were incubated with doxorubicin, gBK was strongly induced, as confirmed by intracellular flow cytometry with a gBK-specific antibody.

Conclusion: Our findings suggested that more immunological targets became available as the tumor responded to chemotherapy and proceeded toward its terminal stages.

No MeSH data available.


Related in: MedlinePlus

gBK expression is induced in HTB119 by doxorubicin. HTB119 cells were cultured for two weeks under the various conditions. The cells were irradiated at Day 0 with 1,000 rad and then cultured. Cells were cultured with cis-platinum, cyclophosphamide, Etoposide or doxorubicin. The cells were lysed, the RNA was isolated and then analyzed for gBK or 18S RNA by qRT-PCR.
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f5: gBK expression is induced in HTB119 by doxorubicin. HTB119 cells were cultured for two weeks under the various conditions. The cells were irradiated at Day 0 with 1,000 rad and then cultured. Cells were cultured with cis-platinum, cyclophosphamide, Etoposide or doxorubicin. The cells were lysed, the RNA was isolated and then analyzed for gBK or 18S RNA by qRT-PCR.

Mentions: We used an HTB119 cell line established from an SCLC patient who had not been subjected to any therapy20,21. This cell line, which expressed minimal gBK protein, represented an initial SCLC case that was not selected because of any clinical intervention8. We collected these HTB119 cells and treated them for 2 weeks with various chemotherapeutic drugs that had been used to treat SCLC22. These cells were examined for gBK expression by qRT-PCR. Figure 5 shows the results of this experiment. Sub-lethal radiation (1,000 rad) and the drugs cisplatinum (50.0 µM), cyclophosphamide (2.5 µM), etoposide (50.0 µM), and doxorubicin (5.0 µM) were examined for their effect on gBK mRNA levels. Cis-platinum, cyclophosphamide, and radiation failed to enhance gBK expression, whereas etoposide gave a slight elevation of gBK (1.5-fold), but this was not considered significantly different from the untreated control values (P=0.084). Doxorubicin displayed an elevated level of gBK transcription (115-fold). This mRNA level proved to be significant between the untreated control SCLC and those treated with doxorubicin (P=0.0001).


Changes in tumor-antigen expression profile as human small-cell lung cancers progress.

Ge LS, Hoa NT, Lambrecht N, Dacosta-Iyer M, Ouyang Y, Abolhoda A, Jadus MR - Cancer Biol Med (2015)

gBK expression is induced in HTB119 by doxorubicin. HTB119 cells were cultured for two weeks under the various conditions. The cells were irradiated at Day 0 with 1,000 rad and then cultured. Cells were cultured with cis-platinum, cyclophosphamide, Etoposide or doxorubicin. The cells were lysed, the RNA was isolated and then analyzed for gBK or 18S RNA by qRT-PCR.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4493377&req=5

f5: gBK expression is induced in HTB119 by doxorubicin. HTB119 cells were cultured for two weeks under the various conditions. The cells were irradiated at Day 0 with 1,000 rad and then cultured. Cells were cultured with cis-platinum, cyclophosphamide, Etoposide or doxorubicin. The cells were lysed, the RNA was isolated and then analyzed for gBK or 18S RNA by qRT-PCR.
Mentions: We used an HTB119 cell line established from an SCLC patient who had not been subjected to any therapy20,21. This cell line, which expressed minimal gBK protein, represented an initial SCLC case that was not selected because of any clinical intervention8. We collected these HTB119 cells and treated them for 2 weeks with various chemotherapeutic drugs that had been used to treat SCLC22. These cells were examined for gBK expression by qRT-PCR. Figure 5 shows the results of this experiment. Sub-lethal radiation (1,000 rad) and the drugs cisplatinum (50.0 µM), cyclophosphamide (2.5 µM), etoposide (50.0 µM), and doxorubicin (5.0 µM) were examined for their effect on gBK mRNA levels. Cis-platinum, cyclophosphamide, and radiation failed to enhance gBK expression, whereas etoposide gave a slight elevation of gBK (1.5-fold), but this was not considered significantly different from the untreated control values (P=0.084). Doxorubicin displayed an elevated level of gBK transcription (115-fold). This mRNA level proved to be significant between the untreated control SCLC and those treated with doxorubicin (P=0.0001).

Bottom Line: Our group has previously observed that in patients with small-cell lung cancers (SCLCs), the expression of a tumor antigen, glioma big potassium (gBK) ion channel, is higher at the time of death than when the cancer is first treated by surgical resection.When HTB119 cells were incubated with doxorubicin, gBK was strongly induced, as confirmed by intracellular flow cytometry with a gBK-specific antibody.Our findings suggested that more immunological targets became available as the tumor responded to chemotherapy and proceeded toward its terminal stages.

View Article: PubMed Central - PubMed

Affiliation: 1 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.

ABSTRACT

Objective: Our group has previously observed that in patients with small-cell lung cancers (SCLCs), the expression of a tumor antigen, glioma big potassium (gBK) ion channel, is higher at the time of death than when the cancer is first treated by surgical resection. This study aimed to determine whether this dichotomy was common in other potential lung tumor antigens by examining the same patient samples using our more extensive profile analysis of tumor-antigen precursor protein (TAPP). We then tested the hypothesis that therapeutic intervention may inadvertently cause this increased gBK production.

Methods: SCLC samples (eight surgical resections and three autopsy samples) and three control lungs were examined by quantitative real-time polymerase chain reaction for 42 potential TAPPs that represent potential T-cell-mediated immunological targets.

Results: Twenty-two TAPP mRNAs displayed the same profile as gBK, i.e., more mRNAs were expressed at autopsy than in their surgical counterparts. B-cyclin and mouse double minute 2, human homolog of P53-binding protein were elevated in both autopsy and surgical specimens above the normal-lung controls. When HTB119 cells were incubated with doxorubicin, gBK was strongly induced, as confirmed by intracellular flow cytometry with a gBK-specific antibody.

Conclusion: Our findings suggested that more immunological targets became available as the tumor responded to chemotherapy and proceeded toward its terminal stages.

No MeSH data available.


Related in: MedlinePlus