Prostate cancer cells preferentially home to osteoblast-rich areas in the early stages of bone metastasis: Evidence from in vivo models

Ning Wang, Freyja E. Docherty, Hannah K. Brown, Kimberley J. Reeves, Anne C.M. Fowles, Penelope D. Ottewell, Terence Neil Dear, Ingunn Holen, Peter I. Croucher, Colby L. Eaton

Research output: Contribution to journalArticle

46 Citations (Scopus)

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 twophoton microscopy to be engrafted in the tibiae in close proximity (40mm) 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.

LanguageEnglish
Pages2688-2696
Number of pages9
JournalJournal of Bone and Mineral Research
Volume29
Issue number12
DOIs
Publication statusPublished - 1 Jan 2014

Keywords

  • Bone metastasis
  • Osteoblast niche
  • Prostate cancer
  • Two-photon microscopy

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

Cite this

Wang, N., Docherty, F. E., Brown, H. K., Reeves, K. J., Fowles, A. C. M., Ottewell, P. D., ... Eaton, C. L. (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), 2688-2696. https://doi.org/10.1002/jbmr.2300
Wang, Ning ; Docherty, Freyja E. ; Brown, Hannah K. ; Reeves, Kimberley J. ; Fowles, Anne C.M. ; Ottewell, Penelope D. ; Dear, Terence Neil ; Holen, Ingunn ; Croucher, Peter I. ; Eaton, Colby L. / Prostate cancer cells preferentially home to osteoblast-rich areas in the early stages of bone metastasis : Evidence from in vivo models. In: Journal of Bone and Mineral Research. 2014 ; Vol. 29, No. 12. pp. 2688-2696.
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Wang, N, Docherty, FE, Brown, HK, Reeves, KJ, Fowles, ACM, Ottewell, PD, Dear, TN, Holen, I, Croucher, PI & Eaton, CL 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, vol. 29, no. 12, pp. 2688-2696. https://doi.org/10.1002/jbmr.2300

Prostate cancer cells preferentially home to osteoblast-rich areas in the early stages of bone metastasis : Evidence from in vivo models. / Wang, Ning; Docherty, Freyja E.; Brown, Hannah K.; Reeves, Kimberley J.; Fowles, Anne C.M.; Ottewell, Penelope D.; Dear, Terence Neil; Holen, Ingunn; Croucher, Peter I.; Eaton, Colby L.

In: Journal of Bone and Mineral Research, Vol. 29, No. 12, 01.01.2014, p. 2688-2696.

Research output: Contribution to journalArticle

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AU - Eaton, Colby L.

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