Vitamin D deficiency promotes prostate cancer growth in bone
Article first published online: 28 DEC 2010
Copyright © 2010 Wiley-Liss, Inc.
Volume 71, Issue 9, pages 1012–1021, 15 June 2011
How to Cite
Zheng, Y., Zhou, H., Ooi, L. L., Snir, A. D., Dunstan, C. R. and Seibel, M. J. (2011), Vitamin D deficiency promotes prostate cancer growth in bone. Prostate, 71: 1012–1021. doi: 10.1002/pros.21316
- Issue published online: 4 MAY 2011
- Article first published online: 28 DEC 2010
- Manuscript Accepted: 8 NOV 2010
- Manuscript Received: 18 JUL 2010
- prostate cancer;
- bone metastasis;
- cancer growth;
- vitamin D deficiency;
Vitamin D is considered as an important determinant of bone turnover as well as cancer growth. Using a murine model of bone metastasis, we investigated the effect of vitamin D deficiency on prostate cancer cell growth in bone.
Three-week-old male nude mice were fed either normal chow (control) or a diet deficient in vitamin D. The latter diet resulted in severe hypovitaminosis D within 6 weeks. At this point of time, 5 × 104 cells of the prostate cancer cell line, PC-3, were injected either into the bone marrow (tibia) or subcutaneously into soft tissues. Osteoprotegerin (OPG) was co-administered in subgroups of mice to suppress bone remodeling. Osteolytic lesions were monitored by serial X-ray, while soft tissue tumor growth was measured by caliper. All tissues were analyzed by micro-CT and histology at endpoint.
Bone turnover was significantly accelerated in vitamin D deficient compared to vitamin D sufficient mice from week 6 onwards. Intra-tibially implanted PC-3 cells resulted in mixed osteolytic and osteosclerotic lesion. At endpoint, osteolytic and osteosclerotic lesion areas, total tumor area, and tumor mitotic activity were all significantly increased in vitamin D deficient mice compared to controls. Regardless of diet, OPG reduced bone turnover, total tumor, and osteosclerotic area as well as tumor mitotic activity, while promoting cell apoptosis. In contrast, vitamin D deficiency did not alter tumor growth in soft tissues.
Vitamin D deficiency stimulates prostate cancer growth in bone through modulating the bone microenvironment. Prostate 71: 1012–1021, 2011. © 2010 Wiley-Liss, Inc.