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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

Twenty-two TAPPs are expressed only within SCLC autopsy samples. Eight surgical resections of SCLC (square symbols), 3 SCLC autopsy samples (triangle symbols) and 3 control lungs samples (circle symbols) from autopsy patients who did not have any cancer were examined for these 22 TAPPs. Asterisks denote significant statistical differences (P<0.05) between the SCLC autopsy and normal lung autopsy values. The data on gBK was previously published in reference 8 and is shown here for comparison purposes with the other antigens.
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f1: Twenty-two TAPPs are expressed only within SCLC autopsy samples. Eight surgical resections of SCLC (square symbols), 3 SCLC autopsy samples (triangle symbols) and 3 control lungs samples (circle symbols) from autopsy patients who did not have any cancer were examined for these 22 TAPPs. Asterisks denote significant statistical differences (P<0.05) between the SCLC autopsy and normal lung autopsy values. The data on gBK was previously published in reference 8 and is shown here for comparison purposes with the other antigens.

Mentions: We collected three control lung samples that did not have cancer, and together with the previously used eight surgically resected SCLC specimens and three SCLC autopsy samples8, we subjected these RNA samples to qRT-PCR analysis. Results showed that for 22 TAPPs, the expression of these antigens was significantly elevated at the time of autopsy, and no or very low expression was observed when the SCLC surgical samples were compared with non-cancerous lung tissue (Figure 1). These potential antigens included the following: antigen isolated from immunoselected melanoma-2, Aim2, antigen recognized by T-cells (ART)-4, calgranulin, carcinoembryonic antigen, cyclophilin B, polycomb group protein enhancer of zeste homolog 2 (EZH2), gBK, melanoma glycoprotein-100 (GP100; also called Pmel 17), livin, Mage-1, Mage-A4, Mage-A10, multidrug-resistance protein-3 (MRP-3), preferentially expressed antigen in melanoma (PRAME), PTH-rP, squamous cell carcinoma ARTs (Sart)-1, Sart-3, the transcription factor Sox2, TARA, hTert, Trp-1, TTR, and Xage-1B. All these TAPP mRNAs were absent from SCLC surgical samples but present in autopsy samples.


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)

Twenty-two TAPPs are expressed only within SCLC autopsy samples. Eight surgical resections of SCLC (square symbols), 3 SCLC autopsy samples (triangle symbols) and 3 control lungs samples (circle symbols) from autopsy patients who did not have any cancer were examined for these 22 TAPPs. Asterisks denote significant statistical differences (P<0.05) between the SCLC autopsy and normal lung autopsy values. The data on gBK was previously published in reference 8 and is shown here for comparison purposes with the other antigens.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f1: Twenty-two TAPPs are expressed only within SCLC autopsy samples. Eight surgical resections of SCLC (square symbols), 3 SCLC autopsy samples (triangle symbols) and 3 control lungs samples (circle symbols) from autopsy patients who did not have any cancer were examined for these 22 TAPPs. Asterisks denote significant statistical differences (P<0.05) between the SCLC autopsy and normal lung autopsy values. The data on gBK was previously published in reference 8 and is shown here for comparison purposes with the other antigens.
Mentions: We collected three control lung samples that did not have cancer, and together with the previously used eight surgically resected SCLC specimens and three SCLC autopsy samples8, we subjected these RNA samples to qRT-PCR analysis. Results showed that for 22 TAPPs, the expression of these antigens was significantly elevated at the time of autopsy, and no or very low expression was observed when the SCLC surgical samples were compared with non-cancerous lung tissue (Figure 1). These potential antigens included the following: antigen isolated from immunoselected melanoma-2, Aim2, antigen recognized by T-cells (ART)-4, calgranulin, carcinoembryonic antigen, cyclophilin B, polycomb group protein enhancer of zeste homolog 2 (EZH2), gBK, melanoma glycoprotein-100 (GP100; also called Pmel 17), livin, Mage-1, Mage-A4, Mage-A10, multidrug-resistance protein-3 (MRP-3), preferentially expressed antigen in melanoma (PRAME), PTH-rP, squamous cell carcinoma ARTs (Sart)-1, Sart-3, the transcription factor Sox2, TARA, hTert, Trp-1, TTR, and Xage-1B. All these TAPP mRNAs were absent from SCLC surgical samples but present in autopsy samples.

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