title: 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 × 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.
  
  
  CONCLUSIONS
  Vitamin D deficiency stimulates prostate cancer growth in bone through modulating the bone microenvironment.
authors.affiliation: Bone Research Program, ANZAC Research Institute, University of Sydney, Concord, Sydney, NSW, Australia.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zheng
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.forename: Li Laine
authors.initials: LL
authors.lastname: Ooi
authors.forename: Afik D
authors.initials: AD
authors.lastname: Snir
authors.forename: Colin R
authors.initials: CR
authors.lastname: Dunstan
authors.forename: Markus J
authors.initials: MJ
authors.lastname: Seibel
mesh_terms: D000135:Acid Phosphatase / Q000097:blood; D000818:Animals; D001859:Bone Neoplasms / Q000097:blood / Q000378:metabolism / Q000556:secondary*; D016723:Bone Remodeling; D002117:Calcitriol / Q000494:pharmacology; D045744:Cell Line, Tumor; D006651:Histocytochemistry; D007527:Isoenzymes / Q000097:blood; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D053244:Osteoprotegerin / Q000378:metabolism; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000378:metabolism / Q000473:pathology*; D013047:Specific Pathogen-Free Organisms; D000071681:Tartrate-Resistant Acid Phosphatase; D014057:Tomography, X-Ray Computed; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood / Q000378:metabolism / Q000473:pathology*
chemical_list: D007527:Isoenzymes; D053244:Osteoprotegerin; D010446:Peptide Fragments; D011347:Procollagen; C047202:procollagen Type I N-terminal peptide; D014807:Vitamin D; C104450:25-hydroxyvitamin D; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D002117:Calcitriol