1,25(OH)2D3 deficiency increases TM40D tumor growth in bone and accelerates tumor-induced bone destruction in a breast cancer bone metastasis model

Biomed Pharmacother. 2017 Nov:95:1033-1039. doi: 10.1016/j.biopha.2017.09.018. Epub 2017 Sep 13.

Abstract

Breast cancer is one of the most common malignancies and bone is the commonest site of distant metastases. Evidences indicate that adequate supply of vitamin D will decrease the morbidity and mortality of breast cancer. However, the main role of vitamin D deficiency in breast cancer bone metastases remains unclear. In this study, the relationship between vitamin D and breast cancer bone metastases were evaluated. Results showed that 1,25(OH)2D3 can not only inhibit the proliferation, migration and invasion of breast cancer cell TM40D in vitro, but also attenuate the breast cancer cell TM40D-induced bone destruction in vivo, whose underlying mechanism was at least partially through decreasing the number of the osteoclasts. To our knowledge, this is the first to use 1-alpha-hydroxylase [1α(OH)ase] knockout mice which characterized vitamin D deficiency to establish the breast cancer bone metastases model. Based on this model, we also found that vitamin D deficiency will accelerate the osteolytic lesions, and 1,25(OH)2D3 supplement will restrain osteolytic lesions. Therefore, these findings suggest that vitamin D has the potential capacity to be a therapeutic agent for the breast cancer bone metastases.

Keywords: 1,25(OH)(2)D(3); Bone metastases; Breast cancer; TM40D; Vicious cycle.

MeSH terms

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase / metabolism
  • Animals
  • Bone Neoplasms / diagnostic imaging
  • Bone Neoplasms / pathology
  • Bone Neoplasms / secondary*
  • Bone Remodeling
  • Bone and Bones / diagnostic imaging
  • Bone and Bones / pathology*
  • Calcitriol / deficiency*
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease Models, Animal
  • Female
  • Mammary Neoplasms, Animal / pathology*
  • Mice
  • Neoplasm Invasiveness
  • Osteolysis / complications
  • Osteolysis / pathology
  • Tartrate-Resistant Acid Phosphatase / metabolism
  • X-Ray Microtomography

Substances

  • 25-Hydroxyvitamin D3 1-alpha-Hydroxylase
  • Tartrate-Resistant Acid Phosphatase
  • Calcitriol