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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

Immunofluorescence microscopy shows 3 TAPPs are present within SCLC specimens taken at autopsy. Three SCLC specimens were examined for expression of h-Tert, Mage-1, and Trp-1 by using antibodies directed towards these 3 TAPPs.
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f3: Immunofluorescence microscopy shows 3 TAPPs are present within SCLC specimens taken at autopsy. Three SCLC specimens were examined for expression of h-Tert, Mage-1, and Trp-1 by using antibodies directed towards these 3 TAPPs.

Mentions: We confirmed the presence of three TAPPs at the protein level within SCLC samples by using antibodies directed against Tert, Mage-1, and Trp-1 proteins. Three archival SCLC histological samples with confirmed distant metastases collected from SCLC patients at the time of their deaths were stained with their respective antibodies, washed, and stained with an FITC-conjugated secondary antibody. All three SCLC samples showed tumors positively stained for these three TAPPs. The representative staining patterns shown in Figure 3 were those of samples collected from a metastatic lesion from the left ventricle. The first column shows the negative controls in which non-immunized IgGs were applied with the appropriate secondary antibody. The middle column shows a non-tumorous region of the left ventricle, and the right column shows the nest of SCLC cells. The top, middle, and bottom rows show Tert, Mage-1, and Trp-1 stainings, respectively. All SCLC cells stained strongly positive. The non-tumorous lung tissue was negative or weakly positive, as proven by their lowered green fluorescence; this internal control showed that the antibody did not stain every cell within the lung.


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)

Immunofluorescence microscopy shows 3 TAPPs are present within SCLC specimens taken at autopsy. Three SCLC specimens were examined for expression of h-Tert, Mage-1, and Trp-1 by using antibodies directed towards these 3 TAPPs.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f3: Immunofluorescence microscopy shows 3 TAPPs are present within SCLC specimens taken at autopsy. Three SCLC specimens were examined for expression of h-Tert, Mage-1, and Trp-1 by using antibodies directed towards these 3 TAPPs.
Mentions: We confirmed the presence of three TAPPs at the protein level within SCLC samples by using antibodies directed against Tert, Mage-1, and Trp-1 proteins. Three archival SCLC histological samples with confirmed distant metastases collected from SCLC patients at the time of their deaths were stained with their respective antibodies, washed, and stained with an FITC-conjugated secondary antibody. All three SCLC samples showed tumors positively stained for these three TAPPs. The representative staining patterns shown in Figure 3 were those of samples collected from a metastatic lesion from the left ventricle. The first column shows the negative controls in which non-immunized IgGs were applied with the appropriate secondary antibody. The middle column shows a non-tumorous region of the left ventricle, and the right column shows the nest of SCLC cells. The top, middle, and bottom rows show Tert, Mage-1, and Trp-1 stainings, respectively. All SCLC cells stained strongly positive. The non-tumorous lung tissue was negative or weakly positive, as proven by their lowered green fluorescence; this internal control showed that the antibody did not stain every cell within the lung.

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