Microenvironmental stress modulates early tumor colonization and CD133 switching in the human metastatic colon cancer cell line, SW620

• Main Authors: Chih-Sin Hsu, 徐志欣
• Other Authors: Chi-Hung Lin
• Format: Others
• Language: en_US
• Published: 2013
• Online Access: http://ndltd.ncl.edu.tw/handle/26788295711429771322

博士 === 國立陽明大學 === 微生物及免疫學研究所 === 101 === Hypothetic models of cancer stem cells have been widely discussed. This subpopulation of cancer cells is thought to play a central role in tumor development, survival, and metastasis. In colon cancer, CD133-positive cells are reported to possess stem-cell–like behavior, include drug-resistance, differentiation, and clonal expansion capabilities; tumor colonization can only be observed in CD133-positive cells. Higher CD133 expression in tumor tissues is associated with metastasis and poor prognosis in colon cancer. However, several reports recently provided evidence that CD133-negative cells from metastatic colon tumors also possess the ability to colonize. These cells even grow larger tumors than CD133-positive cells in a mouse model. These contrasting observations indicated that alternative mechanisms exist. SW620 is a human metastatic colon cancer cell line that contains both CD133-positive and -negative subpopulations. SW620 is an excellent cell model to compare the viability and tumorigenicity of 2 subpopulations with the same genetic background. Our results showed that CD133-negative cells have a growth advantage in early colonization in a mouse model and ex vivo experiments. We also demonstrated that SW620 cells have a bidirectional switch between the CD133-positive and -negative status, and the switching can be modulated by different microenvironment stresses, such as hypoxia, adhesion-free conditions, and extracellular matrix stimulation. Using SW620 cells, we demonstrated that CD133 type switching of colon cancer cells could be induced by environmental stimulation. The type switching might help cancer cells gain a survival advantage in early colonization. Our result provides a novel hypothetic model of colon cancer colonization. The model can provide evidence and possible explains for previous conflicting observations.