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Vitamin D deficiency promotes prostate cancer growth in bone

Abstract

BACKGROUND: 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. METHODS: 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 x 10(4) 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. RESULTS: 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. CONCLUSION: Vitamin D deficiency stimulates prostate cancer growth in bone through modulating the bone microenvironment.

Type Journal
ISBN 1097-0045 (Electronic) 0270-4137 (Linking)
Authors Zheng, Y.; Zhou, H.; Ooi, L. L.; Snir, A. D.; Dunstan, C. R.; Seibel, M. J.;
Publisher Name PROSTATE
Published Date 2011-01-01 00:00:00
Published Volume 71
Published Issue 9
Published Pages 1012-21
URL http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=21541977
Status Published In-print
OpenAccess Link https://publications.gimr.garvan.org.au/download.php?11075_11478/11 Zheng Prostate.pdf