High-CLDN4 ESCC cells harbor stem-like properties and indicate for poor concurrent chemoradiation therapy response in esophageal squamous cell carcinoma

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

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
JournalTherapeutic Advances in Medical Oncology
Volume11
DOIs
Publication statusPublished - 2019 Jan 1

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Stem Cells
Fursultiamin
Neoplasms
Therapeutics
Neoplastic Stem Cells
Esophageal Squamous Cell Carcinoma
Neoplasm Metastasis
Esophageal Neoplasms
Tumor Biomarkers
Treatment Failure
Cisplatin
Survival Rate
Polymerase Chain Reaction

All Science Journal Classification (ASJC) codes

  • Oncology

Cite this

Lin, Cheng Han ; Li, Hao Yi ; Liu, Yu Peng ; Kuo, Pei Fung ; Wang, Wen Ching ; Lin, Forn Chia ; Chang, Wei Lun ; Sheu, Bor Shyang ; Wang, Yi Ching ; Hung, Wan Chun ; Cheng, Hui Chuan ; Yao, Yun Chin ; Calkins, Marcus J. ; Hsiao, Michael ; Lu, Pei Jung. / High-CLDN4 ESCC cells harbor stem-like properties and indicate for poor concurrent chemoradiation therapy response in esophageal squamous cell carcinoma. In: Therapeutic Advances in Medical Oncology. 2019 ; Vol. 11.
@article{e1bf83adb8fa4a2fad06c46ecb3aa39d,
title = "High-CLDN4 ESCC cells harbor stem-like properties and indicate for poor concurrent chemoradiation therapy response in esophageal squamous cell carcinoma",
abstract = "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.",
author = "Lin, {Cheng Han} and Li, {Hao Yi} and Liu, {Yu Peng} and Kuo, {Pei Fung} and Wang, {Wen Ching} and Lin, {Forn Chia} and Chang, {Wei Lun} and Sheu, {Bor Shyang} and Wang, {Yi Ching} and Hung, {Wan Chun} and Cheng, {Hui Chuan} and Yao, {Yun Chin} and Calkins, {Marcus J.} and Michael Hsiao and Lu, {Pei Jung}",
year = "2019",
month = "1",
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High-CLDN4 ESCC cells harbor stem-like properties and indicate for poor concurrent chemoradiation therapy response in esophageal squamous cell carcinoma. / Lin, Cheng Han; Li, Hao Yi; Liu, Yu Peng; Kuo, Pei Fung; Wang, Wen Ching; Lin, Forn Chia; Chang, Wei Lun; Sheu, Bor Shyang; Wang, Yi Ching; Hung, Wan Chun; Cheng, Hui Chuan; Yao, Yun Chin; Calkins, Marcus J.; Hsiao, Michael; Lu, Pei Jung.

In: Therapeutic Advances in Medical Oncology, Vol. 11, 01.01.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - High-CLDN4 ESCC cells harbor stem-like properties and indicate for poor concurrent chemoradiation therapy response in esophageal squamous cell carcinoma

AU - Lin, Cheng Han

AU - Li, Hao Yi

AU - Liu, Yu Peng

AU - Kuo, Pei Fung

AU - Wang, Wen Ching

AU - Lin, Forn Chia

AU - Chang, Wei Lun

AU - Sheu, Bor Shyang

AU - Wang, Yi Ching

AU - Hung, Wan Chun

AU - Cheng, Hui Chuan

AU - Yao, Yun Chin

AU - Calkins, Marcus J.

AU - Hsiao, Michael

AU - Lu, Pei Jung

PY - 2019/1/1

Y1 - 2019/1/1

N2 - 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.

AB - 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.

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