Colon cancer mesenchymal stem cells modulate the tumorigenicity of colon cancer through interleukin 6 |
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Authors: | Jen-Tsun Lin Jeng-Yi Wang Mu-Kuan Chen Hong-Chang Chen Tung-Hao Chang Bi-Wen Su Pey-Jium Chang |
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Affiliation: | 1. Division of Hematology and Oncology, Department of Medicine, Changhua Christian Hospital, Changhua, Taiwan;2. School of Medicine, Chung Shan Medical University, Taichung, Taiwan;3. Graduate School, Feng Chia University, Taichung, Taiwan;4. Division of Colorectal Surgery, Chang Gung Memorial Hospital, LinKo, Taiwan;5. Department of Otorhinolaryngology-Head and Neck Surgery, Changhua Christian Hospital, Changhua, Taiwan;6. Division of Colorectal Surgery, ChangHua Christian Hospital, ChangHua, Taiwan;g Department of Radiation Oncology, ChangHua Christian Hospital, ChangHua, Taiwan;h Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan |
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Abstract: | Multipotent mesenchymal stem cells (MSCs) have been isolated from several tumors and are implicated to play critical roles to increase malignant cell growth, invasion and metastasis. Here, we show that the MSC-like cells were isolated from human colon cancer tissues. These isolated hCC-MSCs (human colon cancer-derived mesenchymal stem cells) shared similar characteristic features with bone marrow-derived MSCs, which include cell morphology, surface antigens and specific gene expression. Additionally, the hCC-MSCs could differentiate into osteocytes or adipocytes under appropriate culture conditions. The conditioned medium collected from the cultured hCC-MSCs was shown to enhance the migration and invasive activity of HCT-116 colon cancer cells in vitro. Besides, transplantation of HCT-116 cells along with hCC-MSCs in nude mice increased the tumor growth and metastasis. Further study revealed that IL-6 present in the hCC-MSC-conditioned medium sufficiently induced the levels of Notch-1 and CD44 in HCT-116 and HT-29 cells, which contribute to enhance tumorigenic activity of HCT-116 and HT-29 cells. By using immunohistochemical staining, the intense co-expression of IL-6, Notch-1 and CD44 was predominantly detected in human colon cancer tissues. Taken together, our findings suggest the importance of the IL-6/Notch-1/CD44 signaling axis in the interaction between hCC-MSCs and colon cancer cells. |
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Keywords: | Colon cancer Mesenchymal stem cells IL-6 Notch-1 CD44 |
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