The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Ĭompeting interests: The authors have declared that no competing interests exist.Ĭolorectal cancer (CRC) is the second most common cancer with 1,234,000 cases worldwide in 2008 according to GLOBOCAN. from Programa de Promoción de la Investigación en Salud del Ministerio de Economía y Competitividad, Instituto de Salud Carlos III (PI10/00428 and PI13/00553) ( ). All data are included within the manuscript.įunding: Supported by grants to A.R.-A. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.ĭata Availability: The authors confirm that all data underlying the findings are fully available without restriction. Received: MaAccepted: Published: June 16, 2014Ĭopyright: © 2014 Lopez-Sánchez et al. Maki, Rush University Medical Center, United States of America (2014) CoCl 2, a Mimic of Hypoxia, Induces Formation of Polyploid Giant Cells with Stem Characteristics in Colon Cancer. The molecular mechanisms involved, including the stabilization of HIF-1 α, the involvement of p53/p47 isoform and cell cycle arrest at G2, suggest novel targets to prevent tumor relapse and treatment failure in colon cancer.Ĭitation: Lopez-Sánchez LM, Jimenez C, Valverde A, Hernandez V, Peñarando J, Martinez A, et al. In conclusion, the pharmacological induction of hypoxia in colon cancer cells causes the formation of PGCCs, the expansion of a cell subpopulation with CSC characteristics and chemoresistance. Generation of PGCCs also contributed to expansion of a cell subpopulation with cancer stem cells (CSCs) characteristics, as indicated by colonosphere formation assays, and enhanced chemoresistance to 5-fluorouracil and oxaliplatin. Furthermore, CoCl 2 treatment effectively induced the stabilization of HIF-1α, the differential expression of a truncated form of p53 (p47) and decreased levels of cyclin D1, indicating molecular mechanisms associated with cell cycle arrest at G2. Polyploidy of hypoxia-induced PGCCs was confirmed by FISH analysis. Cytometric analysis showed that CoCl 2 treatment induced G2 cell cycle arrest and the generation of a polyploid cell subpopulation with increased cellular DNA content. Treatment of HCT-116 and Caco-2 colon cancer cells with the hypoxia mimic CoCl 2 induced the formation of cells with larger cell and nuclear size (PGCCs), while the cells with normal morphology were selectively eliminated. Therefore, the main objective of this study was to investigate the generation of PGCCs in colon cancer cells and identify mechanisms of formation. However, the role of these cells in the development, progression and response to therapy in colon cancer remains undefined. The induction of polyploidy is considered the reproductive end of cells, but there is evidence that polyploid giant cancer cells (PGCCs) contribute to cell repopulation during tumor relapse.
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