Awakening of dormant hematopoietic stem cells
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The often occurring relapse of cancers after initially successful chemo- and radiation therapy is thought to be due to the presence of some therapy resistant cancer stem cells within the original tumor. These malignant stem cells share many characteristics with normal stem cells, which show high resistance to such therapies, too. Marieke Essers and Andreas Trumpp from the German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ) and HI-STEM together with Anne Wilson from the Ludwig Institute of Cancer Research in Lausanne have just published an opinion paper in “Nature Reviews Immunology” proposing a novel model in which hematopoietic stem cells (HSCs) are localized in three different microenvironments called niches, which produce signals that are not only critical to maintain their stem cell self-renewal potential as well as their proliferative activity, but also provide environments that support stem cell function during repair processes initiated after tissue injury. The authors suggest that hematopoietic stem cells (HSCs) dynamically migrate between these three different niches, depending on whether they are dormant or self-renewing during steady-state homeostasis, or whether they are activated and rapidly dividing under conditions of stress. Moreover, they summarize data showing that the most potent HSCs are in a deeply dormant phase during homeostasis, which is accompanied by a striking resistance to chemotherapeutic drugs. Interestingly, three different factors (Granulocyte-Colony-Stimulating-Factor, Interferon-á, and Arsenic-Trioxide) have recently been shown to efficiently activate dormant hematopoietic stem cells and thereby break their resistance to anti-proliferative chemotherapeutics. These data suggest a two-step strategy in which dormant cancer cells need to be activated first before they can be eliminated by chemotherapies. This hypothesis can now be clinically tested for hematological malignancies.
Reference:
Trumpp A, Essers M, Wilson A.
Awakening dormant haematopoietic stem cells.
Nat Rev Immunol. 2010 Mar;10(3):201-9.
PMID: 20182459 doi:10.1038/nri2726