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Plasticity Underlying Multipotent Tumor Stem Cells

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Stem Cells and Cancer

Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

Aggressive cancer cells manifest stem-cell-like qualities that allow them to self-renew and to derive a heterogeneous tumor. Ultimately, this multipotent phenotype facilitates metastasis and resistance to therapy. Cancer cells likely acquire and maintain multipotent phenotypes by aberrantly expressing embryonic factors, such as Nodal and Notch, which maintain pluripotency in normal embryonic stem cell types. Recent studies have shown that Nodal, an embryonic morphogen belonging to the transforming growth factor-beta (TGF-β) superfamily, is aberrantly expressed in melanoma and breast carcinoma cells. Moreover, Nodal facilitates breast cancer and melanoma tumorigenesis. During development, Nodal is regulated by the spatial and temporal expression of inhibitors such as Lefty. In aggressive cancer cells, this balance of regulatory mediators is disrupted, leading to unchecked Nodal expression. By exposing aggressive cancer cells to embryonic microenvironments, inclusive of Lefty, Nodal expression is decreased and tumorigenesis is suppressed. Embryonic stem cell-derived factors, such as Lefty, may provide therapeutic modalities that may be used to specifically differentiate and eradicate aggressive cancers.

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Authors and Affiliations

  1. Children’s Memorial Research Center, Cancer Biology and Epigenomics Program, Robert H. Lurie Comprehensive Cancer Center, Northwestern University’s Feinberg School of Medicine, 60614, Chicago, IL, USA

    Lynne-Marie Postovit, Naira V. Margaryan, Elisabeth A. Seftor, Luigi Strizzi & Richard E.B. Seftor

  2. Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, N6A 5C1, London, ON, Canada

    Mary J.C. Hendrix

Authors
  1. Lynne-Marie Postovit
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  2. Naira V. Margaryan
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  3. Elisabeth A. Seftor
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  4. Luigi Strizzi
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  5. Richard E.B. Seftor
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  6. Mary J.C. Hendrix
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Correspondence to Lynne-Marie Postovit or Mary J.C. Hendrix .

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    Postovit, LM., Margaryan, N.V., Seftor, E.A., Strizzi, L., Seftor, R.E., Hendrix, M.J. (2009). Plasticity Underlying Multipotent Tumor Stem Cells. In: Teicher, B., Bagley, R. (eds) Stem Cells and Cancer. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-60327-933-8_8

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