title: 1α,25-Dihydroxyvitamin D Inhibits the Metastatic Capability of MCF10CA1a and MDA-MB-231 Cells in an In Vitro Model of Breast to Bone Metastasis.
abstract: Breast cancer metastasis to the bone continues to be a major health problem, with approximately 80% of advanced breast cancer patients expected to develop bone metastasis. Although the problem of bone metastasis persists, current treatment options for metastatic cancer patients are limited. In this study, we investigated the preventive role of the active vitamin D metabolite, 1α,25-dihydroxyvitamin D (1,25(OH)2D), against the metastatic potential of breast cancer cells using a novel three-dimensional model (rMET) recapitulating multiple steps of the bone metastatic process. Treatment of MCF10CA1a and MDA-MB-231 cells inhibited metastasis in the rMET model by 70% (±5.7%) and 21% (±6%), respectively. In addition, 1,25(OH)2D treatment decreased invasiveness (20 ± 11% of vehicle) and decreased the capability of MCF10CA1a cells to survive in the reconstructed bone environment after successful invasion through the basement membrane (69 ± 5% of vehicle). An essential step in metastasis is epithelial-mesenchymal transition (EMT). Treatment of MCF10CA1a cells with 1,25(OH)2D increased gene (2.04 ± 0.28-fold increase) and protein (1.87 ± 0.20-fold increase) expression of E-cadherin. Additionally, 1,25(OH)2D treatment decreased N-cadherin gene expression (42 ± 8% decrease), a marker for EMT. Collectively, the present study suggests that 1,25(OH)2D inhibits breast cancer cell metastatic capability as well as inhibits EMT, an essential step in the metastatic process.
authors.affiliation: a Department of Nutrition Science, Interdepartmental Nutrition Program , Purdue University , West Lafayette , Indiana , USA.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Wilmanski
authors.affiliation: a Department of Nutrition Science, Interdepartmental Nutrition Program , Purdue University , West Lafayette , Indiana , USA.
authors.forename: Alle
authors.initials: A
authors.lastname: Barnard
authors.affiliation: b Interdisciplinary Life Science-PULSe , Purdue University , West Lafayette , Indiana , USA.|c Department of Biological Sciences , Purdue University , West Lafayette , Indiana , USA.|d Ixchel Scientific , San Jose , California , USA.
authors.forename: Mukti R
authors.initials: MR
authors.lastname: Parikh
authors.affiliation: c Department of Biological Sciences , Purdue University , West Lafayette , Indiana , USA.|d Ixchel Scientific , San Jose , California , USA.
authors.forename: Julia
authors.initials: J
authors.lastname: Kirshner
authors.affiliation: a Department of Nutrition Science, Interdepartmental Nutrition Program , Purdue University , West Lafayette , Indiana , USA.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Buhman
authors.affiliation: a Department of Nutrition Science, Interdepartmental Nutrition Program , Purdue University , West Lafayette , Indiana , USA.
authors.forename: John
authors.initials: J
authors.lastname: Burgess
authors.affiliation: a Department of Nutrition Science, Interdepartmental Nutrition Program , Purdue University , West Lafayette , Indiana , USA.
authors.forename: Dorothy
authors.initials: D
authors.lastname: Teegarden
mesh_terms: D016588:Anticarcinogenic Agents / Q000378:metabolism / Q000494:pharmacology; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control / Q000556:secondary; D001940:Breast / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D015820:Cadherins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007700:Kinetics; D009361:Neoplasm Invasiveness / Q000473:pathology / Q000517:prevention & control; D009362:Neoplasm Metastasis / Q000473:pathology / Q000517:prevention & control; D009363:Neoplasm Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014807:Vitamin D / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
chemical_list: D016588:Anticarcinogenic Agents; D015703:Antigens, CD; D014408:Biomarkers, Tumor; C513384:CDH1 protein, human; C050361:CDH2 protein, human; D015820:Cadherins; D009363:Neoplasm Proteins; D014807:Vitamin D; C097949:1,25-dihydroxyvitamin D