title: Response to stress in early tumor colonization modulates switching of CD133-positive and CD133-negative subpopulations in a human metastatic colon cancer cell line, SW620.
abstract: According to the cancer stem cell (CSC) model, higher CD133 expression in tumor tissue is associated with metastasis and poor prognosis in colon cancer. As such, the CD133-positive (CD133(+)) subpopulation of cancer cells is believed to play a central role in tumor development and metastatic progression. Although CD133(+) cells are believed to display more CSC-like behavior and be solely responsible for tumor colonization, recent research indicates that CD133(-) cells from metastatic colon tumors not only also possess colonization capacity but also promote the growth of larger tumors in a mouse model than CD133(+) cells, suggesting that an alternative mechanism of metastasis exists. This study investigated this possibility by examining the cell viability, tumorigenicity, and proliferation and growth capacity of the CD133(+) and CD133(-) subpopulations of the SW620 cell line, a human metastatic colon cancer cell line, in both an in vitro cell model and an in vivo mouse model. While both SW620 (CD133-) and SW620(CD133+) cells were found to engage in bidirectional cell-type switching in reaction to exposure to environmental stressors, including hypoxia, a cell adhesion-free environment, and extracellular matrix stimulation, both in vitro and in vivo, CD133(-) cells were found to have a growth advantage during early colonization due to their greater resistance to proliferation inhibition. Based on these findings, a hypothetical model in which colon cancer cells engage in cell-type switching in reaction to exposure to environmental stressors is proposed. Such switching may provide a survival advantage during early colonization, as well as that explain previous conflicting observations.
authors.affiliation: Institute of Microbiology and Immunology, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Chih-Sin
authors.initials: CS
authors.lastname: Hsu
authors.forename: Chien-Yi
authors.initials: CY
authors.lastname: Tung
authors.forename: Chih-Yung
authors.initials: CY
authors.lastname: Yang
authors.forename: Chi-Hung
authors.initials: CH
authors.lastname: Lin
mesh_terms: D000071916:AC133 Antigen; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000473:pathology*; D015972:Gene Expression Regulation, Neoplastic; D006023:Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D010455:Peptides / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013312:Stress, Physiological; D013997:Time Factors; D059016:Tumor Microenvironment
chemical_list: D000071916:AC133 Antigen; D015703:Antigens, CD; D006023:Glycoproteins; C000606023:PROM1 protein, human; D010455:Peptides; C000606024:Prom1 protein, mouse