Characterization of Two Novel Cell Lines with Distinct Heterogeneity Derived from a Single Human Bile Duct Carcinoma

Jinghan Wang, Linfang Li, Keqiang Zhang, Yong Yu, Bin Li, Jiang Li, Zi Yan, Zhenli Hu, Yun Yen, Mengchao Wu, Xiaoqing Jiang, Qijun Qian

研究成果: 雜誌貢獻文章

8 引文 (Scopus)

摘要

Background: Intratumoral heterogeneity reflects subclonal diversity and accounts for a variety of clinically defined phenotypes including the development of drug resistance and recurrence. However, intratumoral heterogeneity of bile duct carcinoma (BDC) is rarely studied. Methods: Two highly heterogeneous cell lines named EH-CA1a and EH-CA1b were established from a primary tumor tissue of a pathologically proven BDC. Distinct heterogeneity and underlying mechanisms of two cell lines in karyotype, colony formation, tumorgenicity, and sensitivity to chemoradiotherapy were intensively studied. Results: Both cell lines showed typical morphology of cancer cells. EH-CA1a cells grew as free-floating aggregates, while EH-CA1b cells grew adherently as a monolayer. EH-CA1a cells had higher cloning efficiencies and were able to keep proliferating under hypoxic condition. Coincidentally, hypoxia-induced factor-1α (HIF1α) and vascular endothelial growth factor (VEGF) mRNA were significantly higher in EH-CA1a cells than in EH-CA1b cells. Both cell lines were tumorigenic in nude mouse, however, EH-CA1a cells showed more aggressive characteristics. Most importantly, the EH-CA1a cells showed much more resistance against radiation and chemotherapy with gemcitabine. Metastasis-related genes including matrix metalloproteinase 2 (MMP-2), MMP-9, epithelial-mesenchymal transition (EMT) markers such as Vimentin, Snail, and Twist, are more highly expressed in EH-CA1a cells than in EH-CA1b cells. Moreover, the percentage of cells expressing cancer stem cell-like marker, CD133, in EH-CA1a cells is much higher than that in EH-CA1b cells. Moreover, knockdown of CD133 in both EH-CA1a and EH-CA1b cells significantly reduced their invasive potential and increased their sensitivities to radiation and gemcitabine, suggesting the differential expression of CD133 protein may partially account for the difference in malignancy between these two cancer cells. Conclusion: Establishment of these two cell lines will not only shed light on intratumoral heterogeneities of BDC, but also potentially facilitate the development of novel therapeutic approaches of BDC.
原文英語
文章編號e54377
期刊PLoS One
8
發行號1
DOIs
出版狀態已發佈 - 一月 30 2013
對外發佈Yes

指紋

bile ducts
Bile Ducts
Ducts
carcinoma
Cells
cell lines
Carcinoma
Cell Line
gemcitabine
cells
Chemoradiotherapy
Radiation
Chemotherapy
Cloning
Matrix Metalloproteinase 2
Vimentin
Stem cells
Matrix Metalloproteinases
Vascular Endothelial Growth Factor A
Neoplasms

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

引用此文

Characterization of Two Novel Cell Lines with Distinct Heterogeneity Derived from a Single Human Bile Duct Carcinoma. / Wang, Jinghan; Li, Linfang; Zhang, Keqiang; Yu, Yong; Li, Bin; Li, Jiang; Yan, Zi; Hu, Zhenli; Yen, Yun; Wu, Mengchao; Jiang, Xiaoqing; Qian, Qijun.

於: PLoS One, 卷 8, 編號 1, e54377, 30.01.2013.

研究成果: 雜誌貢獻文章

Wang, J, Li, L, Zhang, K, Yu, Y, Li, B, Li, J, Yan, Z, Hu, Z, Yen, Y, Wu, M, Jiang, X & Qian, Q 2013, 'Characterization of Two Novel Cell Lines with Distinct Heterogeneity Derived from a Single Human Bile Duct Carcinoma', PLoS One, 卷 8, 編號 1, e54377. https://doi.org/10.1371/journal.pone.0054377
Wang, Jinghan ; Li, Linfang ; Zhang, Keqiang ; Yu, Yong ; Li, Bin ; Li, Jiang ; Yan, Zi ; Hu, Zhenli ; Yen, Yun ; Wu, Mengchao ; Jiang, Xiaoqing ; Qian, Qijun. / Characterization of Two Novel Cell Lines with Distinct Heterogeneity Derived from a Single Human Bile Duct Carcinoma. 於: PLoS One. 2013 ; 卷 8, 編號 1.
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abstract = "Background: Intratumoral heterogeneity reflects subclonal diversity and accounts for a variety of clinically defined phenotypes including the development of drug resistance and recurrence. However, intratumoral heterogeneity of bile duct carcinoma (BDC) is rarely studied. Methods: Two highly heterogeneous cell lines named EH-CA1a and EH-CA1b were established from a primary tumor tissue of a pathologically proven BDC. Distinct heterogeneity and underlying mechanisms of two cell lines in karyotype, colony formation, tumorgenicity, and sensitivity to chemoradiotherapy were intensively studied. Results: Both cell lines showed typical morphology of cancer cells. EH-CA1a cells grew as free-floating aggregates, while EH-CA1b cells grew adherently as a monolayer. EH-CA1a cells had higher cloning efficiencies and were able to keep proliferating under hypoxic condition. Coincidentally, hypoxia-induced factor-1α (HIF1α) and vascular endothelial growth factor (VEGF) mRNA were significantly higher in EH-CA1a cells than in EH-CA1b cells. Both cell lines were tumorigenic in nude mouse, however, EH-CA1a cells showed more aggressive characteristics. Most importantly, the EH-CA1a cells showed much more resistance against radiation and chemotherapy with gemcitabine. Metastasis-related genes including matrix metalloproteinase 2 (MMP-2), MMP-9, epithelial-mesenchymal transition (EMT) markers such as Vimentin, Snail, and Twist, are more highly expressed in EH-CA1a cells than in EH-CA1b cells. Moreover, the percentage of cells expressing cancer stem cell-like marker, CD133, in EH-CA1a cells is much higher than that in EH-CA1b cells. Moreover, knockdown of CD133 in both EH-CA1a and EH-CA1b cells significantly reduced their invasive potential and increased their sensitivities to radiation and gemcitabine, suggesting the differential expression of CD133 protein may partially account for the difference in malignancy between these two cancer cells. Conclusion: Establishment of these two cell lines will not only shed light on intratumoral heterogeneities of BDC, but also potentially facilitate the development of novel therapeutic approaches of BDC.",
author = "Jinghan Wang and Linfang Li and Keqiang Zhang and Yong Yu and Bin Li and Jiang Li and Zi Yan and Zhenli Hu and Yun Yen and Mengchao Wu and Xiaoqing Jiang and Qijun Qian",
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AU - Wang, Jinghan

AU - Li, Linfang

AU - Zhang, Keqiang

AU - Yu, Yong

AU - Li, Bin

AU - Li, Jiang

AU - Yan, Zi

AU - Hu, Zhenli

AU - Yen, Yun

AU - Wu, Mengchao

AU - Jiang, Xiaoqing

AU - Qian, Qijun

PY - 2013/1/30

Y1 - 2013/1/30

N2 - Background: Intratumoral heterogeneity reflects subclonal diversity and accounts for a variety of clinically defined phenotypes including the development of drug resistance and recurrence. However, intratumoral heterogeneity of bile duct carcinoma (BDC) is rarely studied. Methods: Two highly heterogeneous cell lines named EH-CA1a and EH-CA1b were established from a primary tumor tissue of a pathologically proven BDC. Distinct heterogeneity and underlying mechanisms of two cell lines in karyotype, colony formation, tumorgenicity, and sensitivity to chemoradiotherapy were intensively studied. Results: Both cell lines showed typical morphology of cancer cells. EH-CA1a cells grew as free-floating aggregates, while EH-CA1b cells grew adherently as a monolayer. EH-CA1a cells had higher cloning efficiencies and were able to keep proliferating under hypoxic condition. Coincidentally, hypoxia-induced factor-1α (HIF1α) and vascular endothelial growth factor (VEGF) mRNA were significantly higher in EH-CA1a cells than in EH-CA1b cells. Both cell lines were tumorigenic in nude mouse, however, EH-CA1a cells showed more aggressive characteristics. Most importantly, the EH-CA1a cells showed much more resistance against radiation and chemotherapy with gemcitabine. Metastasis-related genes including matrix metalloproteinase 2 (MMP-2), MMP-9, epithelial-mesenchymal transition (EMT) markers such as Vimentin, Snail, and Twist, are more highly expressed in EH-CA1a cells than in EH-CA1b cells. Moreover, the percentage of cells expressing cancer stem cell-like marker, CD133, in EH-CA1a cells is much higher than that in EH-CA1b cells. Moreover, knockdown of CD133 in both EH-CA1a and EH-CA1b cells significantly reduced their invasive potential and increased their sensitivities to radiation and gemcitabine, suggesting the differential expression of CD133 protein may partially account for the difference in malignancy between these two cancer cells. Conclusion: Establishment of these two cell lines will not only shed light on intratumoral heterogeneities of BDC, but also potentially facilitate the development of novel therapeutic approaches of BDC.

AB - Background: Intratumoral heterogeneity reflects subclonal diversity and accounts for a variety of clinically defined phenotypes including the development of drug resistance and recurrence. However, intratumoral heterogeneity of bile duct carcinoma (BDC) is rarely studied. Methods: Two highly heterogeneous cell lines named EH-CA1a and EH-CA1b were established from a primary tumor tissue of a pathologically proven BDC. Distinct heterogeneity and underlying mechanisms of two cell lines in karyotype, colony formation, tumorgenicity, and sensitivity to chemoradiotherapy were intensively studied. Results: Both cell lines showed typical morphology of cancer cells. EH-CA1a cells grew as free-floating aggregates, while EH-CA1b cells grew adherently as a monolayer. EH-CA1a cells had higher cloning efficiencies and were able to keep proliferating under hypoxic condition. Coincidentally, hypoxia-induced factor-1α (HIF1α) and vascular endothelial growth factor (VEGF) mRNA were significantly higher in EH-CA1a cells than in EH-CA1b cells. Both cell lines were tumorigenic in nude mouse, however, EH-CA1a cells showed more aggressive characteristics. Most importantly, the EH-CA1a cells showed much more resistance against radiation and chemotherapy with gemcitabine. Metastasis-related genes including matrix metalloproteinase 2 (MMP-2), MMP-9, epithelial-mesenchymal transition (EMT) markers such as Vimentin, Snail, and Twist, are more highly expressed in EH-CA1a cells than in EH-CA1b cells. Moreover, the percentage of cells expressing cancer stem cell-like marker, CD133, in EH-CA1a cells is much higher than that in EH-CA1b cells. Moreover, knockdown of CD133 in both EH-CA1a and EH-CA1b cells significantly reduced their invasive potential and increased their sensitivities to radiation and gemcitabine, suggesting the differential expression of CD133 protein may partially account for the difference in malignancy between these two cancer cells. Conclusion: Establishment of these two cell lines will not only shed light on intratumoral heterogeneities of BDC, but also potentially facilitate the development of novel therapeutic approaches of BDC.

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