High-CLDN4 ESCC cells harbor stem-like properties and indicate for poor concurrent chemoradiation therapy response in esophageal squamous cell carcinoma
Background: Esophageal squamous cell carcinoma (ESCC) is the major type of esophageal cancer in Asia and demonstrates poor survival rates following a therapeutic regimen. Methods: Cancer stem cells (CSCs) are responsible for tumor initiation, progression, and treatment failure in cancers. Therefore,...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2019-09-01
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| Series: | Therapeutic Advances in Medical Oncology |
| Online Access: | https://doi.org/10.1177/1758835919875324 |
| _version_ | 1818244693412020224 |
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| author | Cheng-Han Lin Hao-Yi Li Yu-Peng Liu Pei-Fung Kuo Wen-Ching Wang Forn-Chia Lin Wei-Lun Chang Bor-Shyang Sheu Yi-Ching Wang Wan-Chun Hung Hui-Chuan Cheng Yun-Chin Yao Marcus J. Calkins Michael Hsiao Pei-Jung Lu |
| author_facet | Cheng-Han Lin Hao-Yi Li Yu-Peng Liu Pei-Fung Kuo Wen-Ching Wang Forn-Chia Lin Wei-Lun Chang Bor-Shyang Sheu Yi-Ching Wang Wan-Chun Hung Hui-Chuan Cheng Yun-Chin Yao Marcus J. Calkins Michael Hsiao Pei-Jung Lu |
| author_sort | Cheng-Han Lin |
| collection | DOAJ |
| description | Background: Esophageal squamous cell carcinoma (ESCC) is the major type of esophageal cancer in Asia and demonstrates poor survival rates following a therapeutic regimen. Methods: Cancer stem cells (CSCs) are responsible for tumor initiation, progression, and treatment failure in cancers. Therefore, identification and characterization of CSCs may help to improve clinical outcomes for ESCC patients. Tumor sphere formation assay are performed to isolate cancer stem-like ESCC cells. QRT-PCR, tumor initiation, metastasis, CCRT treatment are used to evaluate ESCC cells’ stemness properties in vitro and in vivo . Results: The authors’ data demonstrates that cancer stem-like ESCC cells harbored stemness characteristics including self-renewal, differentiation, and transdifferentiation, and possess tumor initiation, metastasis, and treatment inefficiency properties. For the identification of useful biomarkers of cancer stem-like ESCC cells, the authors further identified that CLDN4 was upregulated in cancer stem-like ESCC cells when compared with bulk cancer cells. High-CLDN4 cells harbored stemness and cisplatin/concurrent chemoradiation therapy (CCRT) resistance properties and a high level of CLDN4 was correlated with poor prognosis and poor CCRT response in ESCC patients. Importantly, thiamine tetrahydrofurfuryl disulfide (TTFD) decreased CLDN4 and attenuated stemness in ESCC cells, and TTFD combined with CCRT improved CCRT response in vivo . Conclusions: CLDN4 was suggested as prognostic and a CCRT response indicator for ESCC patients. TTFD combined with CCRT has potential to improve ESCC patient’s clinical outcomes in the future. |
| first_indexed | 2024-12-12T14:21:05Z |
| format | Article |
| id | doaj.art-b18e9d44a0d441e58728c73a619a16f4 |
| institution | Directory Open Access Journal |
| issn | 1758-8359 |
| language | English |
| last_indexed | 2024-12-12T14:21:05Z |
| publishDate | 2019-09-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Therapeutic Advances in Medical Oncology |
| spelling | doaj.art-b18e9d44a0d441e58728c73a619a16f42022-12-22T00:21:47ZengSAGE PublishingTherapeutic Advances in Medical Oncology1758-83592019-09-011110.1177/1758835919875324High-CLDN4 ESCC cells harbor stem-like properties and indicate for poor concurrent chemoradiation therapy response in esophageal squamous cell carcinomaCheng-Han LinHao-Yi LiYu-Peng LiuPei-Fung KuoWen-Ching WangForn-Chia LinWei-Lun ChangBor-Shyang SheuYi-Ching WangWan-Chun HungHui-Chuan ChengYun-Chin YaoMarcus J. CalkinsMichael HsiaoPei-Jung LuBackground: Esophageal squamous cell carcinoma (ESCC) is the major type of esophageal cancer in Asia and demonstrates poor survival rates following a therapeutic regimen. Methods: Cancer stem cells (CSCs) are responsible for tumor initiation, progression, and treatment failure in cancers. Therefore, identification and characterization of CSCs may help to improve clinical outcomes for ESCC patients. Tumor sphere formation assay are performed to isolate cancer stem-like ESCC cells. QRT-PCR, tumor initiation, metastasis, CCRT treatment are used to evaluate ESCC cells’ stemness properties in vitro and in vivo . Results: The authors’ data demonstrates that cancer stem-like ESCC cells harbored stemness characteristics including self-renewal, differentiation, and transdifferentiation, and possess tumor initiation, metastasis, and treatment inefficiency properties. For the identification of useful biomarkers of cancer stem-like ESCC cells, the authors further identified that CLDN4 was upregulated in cancer stem-like ESCC cells when compared with bulk cancer cells. High-CLDN4 cells harbored stemness and cisplatin/concurrent chemoradiation therapy (CCRT) resistance properties and a high level of CLDN4 was correlated with poor prognosis and poor CCRT response in ESCC patients. Importantly, thiamine tetrahydrofurfuryl disulfide (TTFD) decreased CLDN4 and attenuated stemness in ESCC cells, and TTFD combined with CCRT improved CCRT response in vivo . Conclusions: CLDN4 was suggested as prognostic and a CCRT response indicator for ESCC patients. TTFD combined with CCRT has potential to improve ESCC patient’s clinical outcomes in the future.https://doi.org/10.1177/1758835919875324 |
| spellingShingle | Cheng-Han Lin Hao-Yi Li Yu-Peng Liu Pei-Fung Kuo Wen-Ching Wang Forn-Chia Lin Wei-Lun Chang Bor-Shyang Sheu Yi-Ching Wang Wan-Chun Hung Hui-Chuan Cheng Yun-Chin Yao Marcus J. Calkins Michael Hsiao Pei-Jung Lu High-CLDN4 ESCC cells harbor stem-like properties and indicate for poor concurrent chemoradiation therapy response in esophageal squamous cell carcinoma Therapeutic Advances in Medical Oncology |
| title | High-CLDN4 ESCC cells harbor stem-like properties and indicate for poor concurrent chemoradiation therapy response in esophageal squamous cell carcinoma |
| title_full | High-CLDN4 ESCC cells harbor stem-like properties and indicate for poor concurrent chemoradiation therapy response in esophageal squamous cell carcinoma |
| title_fullStr | High-CLDN4 ESCC cells harbor stem-like properties and indicate for poor concurrent chemoradiation therapy response in esophageal squamous cell carcinoma |
| title_full_unstemmed | High-CLDN4 ESCC cells harbor stem-like properties and indicate for poor concurrent chemoradiation therapy response in esophageal squamous cell carcinoma |
| title_short | High-CLDN4 ESCC cells harbor stem-like properties and indicate for poor concurrent chemoradiation therapy response in esophageal squamous cell carcinoma |
| title_sort | high cldn4 escc cells harbor stem like properties and indicate for poor concurrent chemoradiation therapy response in esophageal squamous cell carcinoma |
| url | https://doi.org/10.1177/1758835919875324 |
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