IBMS BoneKEy | Perspective

Cancer stem cells and bone metastasis

Gordon J Strewler



DOI:10.1138/20080335

Abstract

Cancer stem cells, or tumor-initiating cells, are the progenitors of leukemias and the proposed progenitors of solid tumors that metastasize to bone. Stem cells are a small self-renewing population that gives rise to all the other cell types in a tumor. In some cases cancer stem cells arise by oncogenic mutations in somatic stem cells; in other cases mutations in lineage-committed progenitor cells endow them with the stem-cell properties of self-renewal and multipotency. The property of self-renewal requires asymmetric division in order to give rise to one daughter cell with stem cell properties and one that differentiates. Somatic stem cells divide asymmetrically because they reside in a niche; a niche for cancer stem cells has yet to be characterized but probably exists. Cancer stem cells have a motile, prometastatic phenotype and in some cases have undergone epithelial-mesenchymal transition. As tumor progenitors with invasive properties they are strong candidates to be the pioneer cells that initiate metastases, and it is predicted that what limits bone metastasis is the ability of cancer stem cells to find a niche in bone that will support their dormancy and eventual growth. Cells with stem cell properties can be purified for study from several standard breast cancer cell lines and tools exist to investigate the possibility that metastasis of stem cells explains the genesis, dormancy, and chemotherapy-resistance of bone metastases.


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