2016OncotargetOpen access

Role of CD44high/CD133high HCT-116 cells in the tumorigenesis of colon cancer

Jin‐Yong Zhou, Min Chen, Long Ma, Xiaoxiao Wang, Yu-Gen Chen, Shen-Lin Liu

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Abstract

// Jin-Yong Zhou 1, * , Min Chen 2, * , Long Ma 3, * , Xiaoxiao Wang 4 , Yu-Gen Chen 5, * , Shen-Lin Liu 6 1 Central Laboratory, The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, China 2 Department of Internal Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, China 3 Department of Urology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, China 4 Department of Medical Science Research, The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, China 5 Department of Colorectal Surgery, The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, China 6 Department of Oncology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, China * These authors contributed equally to this work Correspondence to: Shen-Lin Liu, e-mail: jsszyylsl@163.com Keywords: CD133, CD44, cancer stem cells (CSCs), colorectal cancer, biomarkers Received: September 24, 2015 Accepted: January 13, 2016 Published: January 30, 2016 ABSTRACT This study aimed to explore cell surface biomarkers related to cancer stem cells (CSCs) and their role in the tumorigenesis of colon cancer. Various colon cancer cell lines were screened for CD133 and CD44 expression. CD44 high /CD133 high and CD44 low /CD133 low cells were separately isolated by Fluorescence-Activated Cell Sorting (FACS). The cell proliferation, colony formation, cell cycle characteristics, and tumorigenic properties in CD44 high /CD133 high and CD44 low /CD133 low cells were investigated through in vitro experiments and in vivo tumor xenograft models. The expression profiles of stem cell-related genes were examined by RT-PCR. With HCT-116 cells, flow cytometry analysis revealed that CD44 high /CD133 high cells had higher proliferation potency than CD44 low /CD133 low cells. Compared to CD44 low /CD133 low cells, CD44 high /CD133 high cells had more stem cell-related genes, and displayed increased tumorigenic ability. In summary, CD44 high /CD133 high cells isolated from HCT-116 cells harbor CSC properties that may be related to the tumor growth of colon cancer. These results suggest that CD44 and CD133 could be strong markers of colorectal cancer stem cells.

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// Jin-Yong Zhou 1, * , Min Chen 2, * , Long Ma 3, * , Xiaoxiao Wang 4 , Yu-Gen Chen 5, * , Shen-Lin Liu 6 1 Central Laboratory, The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, China 2 Department of Internal Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, China 3 Department of Urology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, China 4 Department of Medical Science Research, The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, China 5 Department of Colorectal Surgery, The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, China 6 Department of Oncology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, China * These authors contributed equally to this work Correspondence to: Shen-Lin Liu, e-mail: jsszyylsl@163.com Keywords: CD133, CD44, cancer stem cells (CSCs), colorectal cancer, biomarkers Received: September 24, 2015 Accepted: January 13, 2016 Published: January 30, 2016 ABSTRACT This study aimed to explore cell surface biomarkers related to cancer stem cells (CSCs) and their role in the tumorigenesis of colon cancer. Various colon cancer cell lines were screened for CD133 and CD44 expression. CD44 high /CD133 high and CD44 low /CD133 low cells were separately isolated by Fluorescence-Activated Cell Sorting (FACS). The cell proliferation, colony formation, cell cycle characteristics, and tumorigenic properties in CD44 high /CD133 high and CD44 low /CD133 low cells were investigated through in vitro experiments and in vivo tumor xenograft models. The expression profiles of stem cell-related genes were examined by RT-PCR. With HCT-116 cells, flow cytometry analysis revealed that CD44 high /CD133 high cells had higher proliferation potency than CD44 low /CD133 low cells. Compared to CD44 low /CD133 low cells, CD44 high /CD133 high cells had more stem cell-related genes, and displayed increased tumorigenic ability. In summary, CD44 high /CD133 high cells isolated from HCT-116 cells harbor CSC properties that may be related to the tumor growth of colon cancer. These results suggest that CD44 and CD133 could be strong markers of colorectal cancer stem cells.

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Available abstract

// Jin-Yong Zhou 1, * , Min Chen 2, * , Long Ma 3, * , Xiaoxiao Wang 4 , Yu-Gen Chen 5, * , Shen-Lin Liu 6 1 Central Laboratory, The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, China 2 Department of Internal Medicine, The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, China 3 Department of Urology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, China 4 Department of Medical Science Research, The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, China 5 Department of Colorectal Surgery, The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, China 6 Department of Oncology, The Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Traditional Chinese Medicine, Nanjing, China * These authors contributed equally to this work Correspondence to: Shen-Lin Liu, e-mail: jsszyylsl@163.com Keywords: CD133, CD44, cancer stem cells (CSCs), colorectal cancer, biomarkers Received: September 24, 2015 Accepted: January 13, 2016 Published: January 30, 2016 ABSTRACT This study aimed to explore cell surface biomarkers related to cancer stem cells (CSCs) and their role in the tumorigenesis of colon cancer. Various colon cancer cell lines were screened for CD133 and CD44 expression. CD44 high /CD133 high and CD44 low /CD133 low cells were separately isolated by Fluorescence-Activated Cell Sorting (FACS). The cell proliferation, colony formation, cell cycle characteristics, and tumorigenic properties in CD44 high /CD133 high and CD44 low /CD133 low cells were investigated through in vitro experiments and in vivo tumor xenograft models. The expression profiles of stem cell-related genes were examined by RT-PCR. With HCT-116 cells, flow cytometry analysis revealed that CD44 high /CD133 high cells had higher proliferation potency than CD44 low /CD133 low cells. Compared to CD44 low /CD133 low cells, CD44 high /CD133 high cells had more stem cell-related genes, and displayed increased tumorigenic ability. In summary, CD44 high /CD133 high cells isolated from HCT-116 cells harbor CSC properties that may be related to the tumor growth of colon cancer. These results suggest that CD44 and CD133 could be strong markers of colorectal cancer stem cells.

Key concepts: Carcinogenesis, Colorectal cancer, Cancer research, Cancer, Medicine, Oncology, Biology, Internal medicine

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Role of CD44high/CD133high HCT-116 cells in the tumorigenesis of colon cancer — Research Paper | ScholarLens