Bone turnover mediates preferential localization of prostate cancer in the skeleton

Abraham Schneider, Linda M. Kalikin, Ana C. Mattos, Evan T. Keller, Matthew J. Allen, Kenneth Pienta, Laurie K. McCauley

Research output: Contribution to journalArticle

Abstract

Bone metastasis is a common untreatable complication associated with prostate cancer. Metastatic cells seed in skeletal sites under active turnover containing dense marrow cellularity. We hypothesized that differences in these skeletal-specific processes are among the critical factors that facilitate the preferential localization of metastatic prostate cancer in bone. To test this, athymic mice were administered PTH to induce bone turnover and increase marrow cellularity daily 1 wk before and after intracardiac inoculation of luciferase-tagged PC-3 cells. Tumor localization was monitored by bioluminescence imaging weekly for 5 wk. At the time of tumor inoculation, PTH-treated mice demonstrated significant increases in serum levels of bone turnover markers such as osteocalcin and tartrate-resistant acid phosphatase 5b and in the number of tartrate-resistant acid phosphatase-positive osteoclasts per millimeter of bone when compared with the other groups. Likewise, PTH treatment stimulated a qualitative increase in marrow cellular proliferation as determined by 5-bromo-2′-deoxyuridine immunostaining. Skeletal metastases formed in the hind limb and craniofacial regions of young mice with no difference between groups. In adult mice, however, bioluminescent signals in the hind limb and craniofacial regions were 3-fold higher in PTH-treated mice vs. controls. Fluorochrome labeling revealed increased bone formation activity in trabecular bone adjacent to tumors. When zoledronic acid, a nitrogen-containing bisphosphonate that inhibits osteoclast-mediated bone resorption, was administered concurrently with PTH, a significant reduction in the incidence of bone tumors was observed. Overall, these studies provide new evidence that skeletal sites rich in marrow cellularity under active turnover offer a more congenial microenvironment to facilitate cancer localization in the skeleton.

Original languageEnglish (US)
Pages (from-to)1727-1736
Number of pages10
JournalEndocrinology
Volume146
Issue number4
DOIs
StatePublished - Apr 2005
Externally publishedYes

Fingerprint

Bone Remodeling
Skeleton
Prostatic Neoplasms
Bone Marrow
zoledronic acid
Osteoclasts
Neoplasms
Bone and Bones
Extremities
Neoplasm Metastasis
Bone Neoplasms
Osteocalcin
Diphosphonates
Bromodeoxyuridine
Bone Resorption
Luciferases
Fluorescent Dyes
Osteogenesis
Nude Mice
Catalytic Domain

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Cite this

Schneider, A., Kalikin, L. M., Mattos, A. C., Keller, E. T., Allen, M. J., Pienta, K., & McCauley, L. K. (2005). Bone turnover mediates preferential localization of prostate cancer in the skeleton. Endocrinology, 146(4), 1727-1736. https://doi.org/10.1210/en.2004-1211

Bone turnover mediates preferential localization of prostate cancer in the skeleton. / Schneider, Abraham; Kalikin, Linda M.; Mattos, Ana C.; Keller, Evan T.; Allen, Matthew J.; Pienta, Kenneth; McCauley, Laurie K.

In: Endocrinology, Vol. 146, No. 4, 04.2005, p. 1727-1736.

Research output: Contribution to journalArticle

Schneider, A, Kalikin, LM, Mattos, AC, Keller, ET, Allen, MJ, Pienta, K & McCauley, LK 2005, 'Bone turnover mediates preferential localization of prostate cancer in the skeleton', Endocrinology, vol. 146, no. 4, pp. 1727-1736. https://doi.org/10.1210/en.2004-1211
Schneider, Abraham ; Kalikin, Linda M. ; Mattos, Ana C. ; Keller, Evan T. ; Allen, Matthew J. ; Pienta, Kenneth ; McCauley, Laurie K. / Bone turnover mediates preferential localization of prostate cancer in the skeleton. In: Endocrinology. 2005 ; Vol. 146, No. 4. pp. 1727-1736.
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