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Metabolic restriction of cancer cells in vitro causes karyotype contraction—an indicator of cancer promotion?

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Tumor Biology

Abstract

The metabolism of cultured cancer cells is stimulated by 21% oxygen and generous nutrition, while real tumors grow in oxygen and nutrient-restricted environments. The effect of these contrasted conditions was studied in five hyperploid (54–69) cancer cell lines. When grown under anoxia and in the presence of antioxidant metabolic restrictors, the cell lines quickly reverted to almost normal chromosome numbers (47–49). The stepped withdrawal of oxygen over K562 showed progressive increases in proliferation rate and the acquisition of a stable, stem phenotype. In genetic studies, hyperploid cancer cells adjusted their chromosome numbers up or down to match their micro-environment through rapid mechanisms of endo-reduplication or chromosome loss. These fast reactions may explain the surprising adaptability of tumor cells to oncologic interventions. Furthermore, karyotype contraction may provide a basis for the previously observed carcinogenic influence of the administration of some antioxidants in human populations.

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Acknowledgments

We are grateful to Janet Moir and Lorne Beckman of the Royal Victoria Hospital. We are indebted to Josée Hébert, Sylvie Lavallée, and Claude Rondeau, Immunology and Cancer Research Institute of Maisonneuve-Rosemont Hospital. We thank Drs. Zhang Guo Chen and Ju Yan for reviewing the paper. The work was supported by Royal Victoria Hospital Research Institute Fund 65891.

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  1. InVitroPlus Laboratory, Department of Surgery, Royal Victoria Hospital, Montreal, Canada

    Ying Li & Paul Héroux

  2. Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Canada

    Ying Li & Paul Héroux

  3. Cell Culture Technologies, Toronto, Ontario, Canada

    Igor Kyrychenko

  4. Faculty of Medicine, McGill University, 1110 Pine Ave West, Montreal, Canada, H3A 1A3

    Paul Héroux

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Li, Y., Héroux, P. & Kyrychenko, I. Metabolic restriction of cancer cells in vitro causes karyotype contraction—an indicator of cancer promotion?. Tumor Biol. 33, 195–205 (2012). https://doi.org/10.1007/s13277-011-0262-6

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