Vitamin D deficiency promotes growth of MCF-7 human breast cancer in a rodent model of osteosclerotic bone metastasis

Bone. 2010 Oct;47(4):795-803. doi: 10.1016/j.bone.2010.07.012. Epub 2010 Jul 16.


Introduction: Breast cancer metastases to bone are common in advanced stage disease. We have recently demonstrated that vitamin D deficiency enhances breast cancer growth in an osteolytic mouse model of breast cancer metastasis. In this study, we examined the effects of vitamin D deficiency on tumor growth in an osteosclerotic model of intra-skeletal breast cancer in mice.

Methods: The effects of 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] on proliferation and apoptosis of MCF-7 breast cancer cells, and changes in the expression of genes within the vitamin D metabolic pathway (VDR, 1α- and 24-hydroxylase) were examined in vitro. MCF-7 breast cancer cells were injected intra-tibially into vitamin D deficient and vitamin D sufficient mice co-treated with and without osteoprotegerin (OPG). The development of tumor-related lesions was monitored via serial X-ray analysis. Tumor burden and indices of proliferation and apoptosis were determined by histology along with markers of bone turnover and serum intact PTH levels.

Results: In vitro, MCF-7 cells expressed critical genes for vitamin D signalling and metabolism. Treatment with 1,25(OH)(2)D(3) inhibited cell growth and proliferation, and increased apoptosis. In vivo, osteosclerotic lesions developed faster and were larger at endpoint in the tibiae of vitamin D deficient mice compared to vitamin D sufficient mice (1.49±0.08 mm(2) versus 1.68±0.15 mm(2), P<0.05). Tumor area was increased by 55.8% in vitamin D deficient mice (0.81±0.13 mm(2) versus 0.52±0.11 mm(2) in vitamin D sufficient mice). OPG treatment inhibited bone turnover and caused an increase in PTH levels, while tumor burden was reduced by 90.4% in vitamin D sufficient mice and by 92.6% in vitamin D deficient mice. Tumor mitotic activity was increased in the tibiae of vitamin D deficient mice and apoptosis was decreased, consistent with faster growth.

Conclusion: Vitamin D deficiency enhances both the growth of tumors and the tumor-induced osteosclerotic changes in the tibiae of mice following intratibial implantation of MCF-7 cells. Enhancement of tumor growth appears dependent on increased bone resorption rather than increased bone formation induced by these tumors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acid Phosphatase / metabolism
  • Adipose Tissue / drug effects
  • Adipose Tissue / pathology
  • Animals
  • Apoptosis / drug effects
  • Bone Neoplasms / complications*
  • Bone Neoplasms / diagnostic imaging
  • Bone Neoplasms / physiopathology
  • Bone Neoplasms / secondary*
  • Bone Remodeling / drug effects
  • Bone and Bones / drug effects
  • Bone and Bones / pathology
  • Bone and Bones / physiopathology
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology*
  • Calcitriol / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Disease Models, Animal
  • Disease Progression
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Isoenzymes / metabolism
  • Mice
  • Osteolysis / complications
  • Osteolysis / pathology
  • Osteosclerosis / complications*
  • Osteosclerosis / enzymology
  • Osteosclerosis / pathology
  • Radiography
  • Tartrate-Resistant Acid Phosphatase
  • Tumor Burden / drug effects
  • Vitamin D Deficiency / complications*
  • Vitamin D Deficiency / pathology
  • Xenograft Model Antitumor Assays*


  • Isoenzymes
  • Acid Phosphatase
  • Tartrate-Resistant Acid Phosphatase
  • Calcitriol