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    Mitotic quiescence, but not unique "stemness," marks the phenotype of bone metastasis-initiating cells in prostate cancer.

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    Authors
    Wang, N
    Docherty, F
    Brown, H
    Reeves, Kimberley J
    Fowles, A
    Lawson, M
    Ottewell, P
    Holen, I
    Croucher, P
    Eaton, C
    Affiliation
    Department of Human Metabolism, Medical School, University of Sheffield, Sheffield
    Issue Date
    2015-04-17
    
    Metadata
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    Abstract
    This study aimed to identify subpopulations of prostate cancer cells that are responsible for the initiation of bone metastases. Using rapidly dividing human prostate cancer cell lines, we identified mitotically quiescent subpopulations (<1%), which we compared with the rapidly dividing populations for patterns of gene expression and for their ability to migrate to the skeletons of athymic mice. The study used 2-photon microscopy to map the presence/distribution of fluorescently labeled, quiescent cells and luciferase expression to determine the presence of growing bone metastases. We showed that the mitotically quiescent cells were very significantly more tumorigenic in forming bone metastases than fast-growing cells (55 vs. 15%) and had a unique gene expression profile. The quiescent cells were not uniquely stem cell like, with no expression of CD133 but had the same level expression of other putative prostate stem cell markers (CD44 and integrins α2/β1), when compared to the rapidly proliferating population. In addition, mitotic quiescence was associated with very high levels of C-X-C chemokine receptor type 4 (CXCR4) production. Inhibition of CXCR4 activity altered the homing of quiescent tumor cells to bone. Our studies suggest that mitotic dormancy is a unique phenotype that facilitates tumor cell colonization of the skeleton in prostate cancer.-Wang, N., Docherty, F., Brown, H. K., Reeves, K., Fowles, A., Lawson, M., Ottewell, P. D., Holen, I., Croucher, P. I., Eaton, C. L. Mitotic quiescence, but not unique "stemness," marks the phenotype of bone metastasis-initiating cells in prostate cancer.
    Citation
    Mitotic quiescence, but not unique "stemness," marks the phenotype of bone metastasis-initiating cells in prostate cancer. 2015: FASEB J
    Journal
    FASEB Journal
    URI
    http://hdl.handle.net/10541/555776
    DOI
    10.1096/fj.14-266379
    PubMed ID
    25888599
    Type
    Article
    Language
    en
    ISSN
    1530-6860
    ae974a485f413a2113503eed53cd6c53
    10.1096/fj.14-266379
    Scopus Count
    Collections
    All Paterson Institute for Cancer Research

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