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The role of cell differentiation in controlling cell multiplication and cancer

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Abstract

It has been suggested that cancer ought to be regarded as a disease of cell differentiation. In multicellular organisms, indeed, the control of cell multiplication is linked to cell specialization: During the process of differentiation embryonic cells, while cycling, acquire the ability to perform specialized functions. This ability is incompatible with cell cycling which, as a consequence, is repressed with forthcoming differentiation. Thus, the number of amplification divisions that occur during the period while differentiation is proceeding decides on the number of specialized cells produced. The progress in differentiation, contrary to usual assumptions, is accompanied by an increase in the cellular content of cytoplasm. The reason must be that cell specialization requires a specific amount and array of membrane-bounded cytoplasmic structures. Since the multiplication of these structures depends on membranous templates, their amount increases only if more cytoplasm is produced per cycle than required for a doubling, thus constituting an intracellular timer of differentiation: The larger the net rate of cytoplasmic growth per cell cycle, the fewer cycles occur. Extracellular signals modulate cell multiplication by altering the net rate of cytoplasmic growth. Each persisting alteration, however, that reduces this rate to zero, prevents differentiation, and thus causes the cells to retain embryonic capabilities and to initiate cancer. Cancer cells can be induced to differentiate and cease proliferation by support of cytoplasmic growth. This corroborates the suggestion that cancer must be regarded as a disease of cell differentiation and our conclusion that cancer is caused by a deficiency in cytoplasmic growth. Support of the latter must be an efficient principle in cancer therapy although limited by the organism’s dependence on cell renewal.

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Acknowledgments

We are indebted to K. Zilles for support of these investigations and to G. Michaelis and T. Lisowski for earlier information on the capabilities of mitochondria.

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  1. Hans-Peter Peterson

    Present address: Division BIO, Project Management Organization, Research Center Jülich, 52425, Jülich, Germany

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  1. Institute of Medicine, Research Center Jülich, 52425, Jülich, Germany

    Karl-Hartmut von Wangenheim & Hans-Peter Peterson

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Correspondence to Karl-Hartmut von Wangenheim.

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von Wangenheim, KH., Peterson, HP. The role of cell differentiation in controlling cell multiplication and cancer. J Cancer Res Clin Oncol 134, 725–741 (2008). https://doi.org/10.1007/s00432-008-0381-7

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