1α,25‐dihydroxyvitamin D3 Inhibits Matrix Metalloprotease 2 Expression in Metastatic Breast Cancer Cells

Abstract

Breast cancer remains the second leading cause of cancer death among women in the United States. When the tumor is localized, 99% of breast cancer patients survive five years after diagnosis. However, if the tumor has metastasized to distant secondary organs, the survival rate drastically decreases to 22%. Epidemiological and animal studies support the hypothesis that vitamin D may inhibit breast cancer metastasis, but the mechanisms remain unknown. The purpose of the present studies was to investigate the effect of the bioactive vitamin D metabolite, 1α,25‐dihydroxyvitamin D3 (1,25(OH)2D) on expression of Matrix Metalloproteinases (MMP) in MCF10CA1a breast epithelial cells. MMPs are a family of endopeptidases implicated in both cancer cell invasion and migration. First, the pattern of MMP expression in MCF10CA1a cells was investigated focusing on MMPs 1,2,3,9 and 13. MCF10CA1a cells expressed only MMP2 mRNA at a detectable level. Treatment with 1,25(OH)2D (10 nM,) reduced the expression of MMP2 by 32%±10 and 35%±7 at 2 and 5 days, respectively. Furthermore, the effect of 1,25(OH)2D on migratory capability of MCF10CA1a cells was assessed using a wound heal assay. Pretreatment with 1,25(OH)2D for 48 hours decreased cell migration by 44%±9.6 relative to vehicle. Further studies are needed to evaluate a causal link between vitamin D mediated downregulation of MMP2 and the nutrient's inhibition of breast cancer cell migration.Support or Funding InformationThis work was supported by a Project Development Team within the ICTSI NIH/NCRR (Grant Number UL1TR001108) and the National Institutes of Health, National Cancer Institute (R25CA128770) Cancer Prevention Internship Program. Additional support was received from the Indiana Elks Charities and the SIRG grant, both administered through the Purdue University Center for Cancer Research (Purdue University, West Lafayette, IN).