Wang, N., Docherty, F.E., Brown, H.K. et al. (7 more authors) (2014) Prostate Cancer Cells Preferentially Home to Osteoblast-rich Areas in the Early Stages of Bone Metastasis: Evidence From In Vivo Models. Journal of Bone and Mineral Research , 29 (12). pp. 2688-2696. ISSN 0884-0431
Abstract
It has been suggested that metastasis-initiating cells gain a foothold in bone by homing to a metastastatic microenvironment (or “niche”). Whereas the precise nature of this niche remains to be established, it is likely to contain bone cell populations including osteoblasts and osteoclasts. In the mouse tibia, the distribution of osteoblasts on endocortical bone surfaces is non-uniform, and we hypothesize that studying co-localization of individual tumor cells with resident cell populations will reveal the identity of critical cellular components of the niche. In this study, we have mapped the distribution of three human prostate cancer cell lines (PC3-NW1, LN-CaP, and C4 2B4) colonizing the tibiae of athymic mice following intracardiac injection and evaluated their interaction with potential metastatic niches. Prostate cancer cells labeled with the fluorescent cell membrane dye (Vybrant DiD) were found by two-photon microscopy to be engrafted in the tibiae in close proximity (∼40 µm) to bone surfaces and 70% more cancer cells were detected in the lateral compared to the medial endocortical bone regions. This was associated with a 5-fold higher number of osteoblasts and 7-fold higher bone formation rate on the lateral endocortical bone surface compared to the medial side. By disrupting cellular interactions mediated by the chemokine (C-X-C motif) receptor 4 (CXCR4)/chemokine ligand 12 (CXCL12) axis with the CXCR4 inhibitor AMD3100, the preferential homing pattern of prostate cancer cells to osteoblast-rich bone surfaces was disrupted. In this study, we map the location of prostate cancer cells that home to endocortical regions in bone and our data demonstrate that homing of prostate cancer cells is associated with the presence and activity of osteoblast lineage cells, and suggest that therapies targeting osteoblast niches should be considered to prevent development of incurable prostate cancer bone metastases.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2014 American Society for Bone and Mineral Research. This is an author produced version of a paper subsequently published in Journal of Bone and Mineral Research. Uploaded in accordance with the publisher's self-archiving policy. |
Keywords: | PROSTATE CANCER; BONE METASTASIS; OSTEOBLAST NICHE; TWO-PHOTON MICROSCOPY |
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 |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 22 Apr 2016 14:00 |
Last Modified: | 03 Nov 2017 03:38 |
Published Version: | http://dx.doi.org/10.1002/jbmr.2300 |
Status: | Published |
Publisher: | American Society for Bone and Mineral Research |
Refereed: | Yes |
Identification Number: | 10.1002/jbmr.2300 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:97676 |