Wang, N., Docherty, F., Brown, H.K. et al. (7 more authors) (2015) Mitotic quiescence, but not unique "stemness," marks the phenotype of bone metastasis-initiating cells in prostate cancer. FASEB Journal, 29 (8). pp. 3141-3150. ISSN 0892-6638
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2015 FASEB. This is an author produced version of a paper subsequently published in FASEB Journal. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | Cell quiescence; CXCR4; metastatic niche |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > Department of Human Metabolism (Sheffield) The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology and Metabolism (Sheffield) The University of Sheffield > Sheffield Teaching Hospitals |
Funding Information: | Funder Grant number CANCER RESEARCH UK (CRUK) C13324/A11991 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 05 May 2016 14:13 |
Last Modified: | 07 May 2016 15:41 |
Published Version: | http://dx.doi.org/10.1096/fj.14-266379 |
Status: | Published |
Publisher: | Federation of American Society of Experimental Biology |
Identification Number: | 10.1096/fj.14-266379 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:97674 |