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EpCAM expression in esophageal cancer and its correlation with immunotherapy of solitomab

BACKGROUND: Recurrence of esophageal cancer (EC) after chemotherapy may mainly be explained by the existence of chemotherapy-resistant cells, and an effective drug against chemotherapy-resistant cells is highly sought. The aim of this study was to investigate the cytotoxicity of bispecific antibody...

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Autores principales: Yu, Lan, Guo, Qing-Ming, Wang, Yu, Xu, Yan, Liu, Li, Zhang, Xiao-Tao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: AME Publishing Company 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107559/
https://www.ncbi.nlm.nih.gov/pubmed/34012588
http://dx.doi.org/10.21037/jtd-21-442
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author Yu, Lan
Guo, Qing-Ming
Wang, Yu
Xu, Yan
Liu, Li
Zhang, Xiao-Tao
author_facet Yu, Lan
Guo, Qing-Ming
Wang, Yu
Xu, Yan
Liu, Li
Zhang, Xiao-Tao
author_sort Yu, Lan
collection PubMed
description BACKGROUND: Recurrence of esophageal cancer (EC) after chemotherapy may mainly be explained by the existence of chemotherapy-resistant cells, and an effective drug against chemotherapy-resistant cells is highly sought. The aim of this study was to investigate the cytotoxicity of bispecific antibody solitomab combined with γ δ T cells on Eca109 cell spheres. METHODS: We cultured Eca109 cell spheres in serum-free medium, and the morphological differences between wild-type Eca109 cells and Eca109 cell spheres were compared by microscope and flow cytometry. Different concentrations of nanoparticle albumin-bound paclitaxel (Nab-PTX) and cisplatin were used to treat the two groups of cells and compare their drug resistance. Flow cytometry was then used to detect the expression level of epithelial cell adhesion molecule (EpCAM) and the cytotoxicity of γ δ T cells combined with bispecific antibody solitomab on the two groups. RESULTS: Flow cytometry analysis showed that Eca109 cell spheres were smaller in size and had less cytoplasmic granules and CCK-8 assay showed that the viability of Eca109 cell spheres treated with different concentrations of Nab-PTX and cisplatin was significantly higher than that of wild-type Eca109 cells (P<0.05). Flow cytometry also showed that the expression level of EpCAM on Eca109 cell spheres was higher than that of wild-type Eca109 cells. Co-culture experiment showed that there was no significant difference in the cytotoxicity of γ δ T cells to wild-type Eca109 cells and Eca109 cell spheres without solitomab. However, after adding solitomab, the cytotoxicity of γ δ T cells to Eca109 cell spheres was significantly higher than that of wild-type Eca109 cells (P<0.05). CONCLUSIONS: EC Eca109 cell spheres have strong stem cell characteristics such as multidrug resistance and may contain a high proportion of EC stem cells. Further, EC Eca109 cell spheres have a high expression level of EpCAM, and EpCAM may be one of the markers of EC stem cells. Therefore, EpCAM could be used as a potential molecular target of immunotherapy for EC, and solitomab may become an effective immunotherapeutic drug for chemotherapy-resistant EC cells.
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spelling pubmed-81075592021-05-18 EpCAM expression in esophageal cancer and its correlation with immunotherapy of solitomab Yu, Lan Guo, Qing-Ming Wang, Yu Xu, Yan Liu, Li Zhang, Xiao-Tao J Thorac Dis Original Article BACKGROUND: Recurrence of esophageal cancer (EC) after chemotherapy may mainly be explained by the existence of chemotherapy-resistant cells, and an effective drug against chemotherapy-resistant cells is highly sought. The aim of this study was to investigate the cytotoxicity of bispecific antibody solitomab combined with γ δ T cells on Eca109 cell spheres. METHODS: We cultured Eca109 cell spheres in serum-free medium, and the morphological differences between wild-type Eca109 cells and Eca109 cell spheres were compared by microscope and flow cytometry. Different concentrations of nanoparticle albumin-bound paclitaxel (Nab-PTX) and cisplatin were used to treat the two groups of cells and compare their drug resistance. Flow cytometry was then used to detect the expression level of epithelial cell adhesion molecule (EpCAM) and the cytotoxicity of γ δ T cells combined with bispecific antibody solitomab on the two groups. RESULTS: Flow cytometry analysis showed that Eca109 cell spheres were smaller in size and had less cytoplasmic granules and CCK-8 assay showed that the viability of Eca109 cell spheres treated with different concentrations of Nab-PTX and cisplatin was significantly higher than that of wild-type Eca109 cells (P<0.05). Flow cytometry also showed that the expression level of EpCAM on Eca109 cell spheres was higher than that of wild-type Eca109 cells. Co-culture experiment showed that there was no significant difference in the cytotoxicity of γ δ T cells to wild-type Eca109 cells and Eca109 cell spheres without solitomab. However, after adding solitomab, the cytotoxicity of γ δ T cells to Eca109 cell spheres was significantly higher than that of wild-type Eca109 cells (P<0.05). CONCLUSIONS: EC Eca109 cell spheres have strong stem cell characteristics such as multidrug resistance and may contain a high proportion of EC stem cells. Further, EC Eca109 cell spheres have a high expression level of EpCAM, and EpCAM may be one of the markers of EC stem cells. Therefore, EpCAM could be used as a potential molecular target of immunotherapy for EC, and solitomab may become an effective immunotherapeutic drug for chemotherapy-resistant EC cells. AME Publishing Company 2021-04 /pmc/articles/PMC8107559/ /pubmed/34012588 http://dx.doi.org/10.21037/jtd-21-442 Text en 2021 Journal of Thoracic Disease. All rights reserved. https://creativecommons.org/licenses/by-nc-nd/4.0/Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0 (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle Original Article
Yu, Lan
Guo, Qing-Ming
Wang, Yu
Xu, Yan
Liu, Li
Zhang, Xiao-Tao
EpCAM expression in esophageal cancer and its correlation with immunotherapy of solitomab
title EpCAM expression in esophageal cancer and its correlation with immunotherapy of solitomab
title_full EpCAM expression in esophageal cancer and its correlation with immunotherapy of solitomab
title_fullStr EpCAM expression in esophageal cancer and its correlation with immunotherapy of solitomab
title_full_unstemmed EpCAM expression in esophageal cancer and its correlation with immunotherapy of solitomab
title_short EpCAM expression in esophageal cancer and its correlation with immunotherapy of solitomab
title_sort epcam expression in esophageal cancer and its correlation with immunotherapy of solitomab
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8107559/
https://www.ncbi.nlm.nih.gov/pubmed/34012588
http://dx.doi.org/10.21037/jtd-21-442
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