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Vitamin D deficiency promotes prostate cancer growth in bone
Author(s) -
Zheng Yu,
Zhou Hong,
Ooi Li Laine,
Snir Afik D.,
Dunstan Colin R.,
Seibel Markus J.
Publication year - 2010
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.21316
Subject(s) - prostate cancer , medicine , bone remodeling , endocrinology , bone metastasis , vitamin d deficiency , cancer , vitamin d and neurology , prostate
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 × 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. Prostate 71: 1012–1021, 2011. © 2010 Wiley‐Liss, Inc.