title: Regulation of motility, invasion, and metastatic potential of squamous cell carcinoma by 1α,25-dihydroxycholecalciferol.
abstract: BACKGROUND
  The active metabolite of vitamin D 1α,25-dihydroxycholecalciferol (1,25D(3) ) has exhibited broad-spectrum antitumor activity in xenograft animal models. However, its activity against metastatic disease has not been extensively investigated.
  
  
  METHODS
  Squamous cell carcinoma (SCC) or 1,25D(3) -resistant variant SCC-DR cells were treated with 1,25D(3) . Actin organization was examined by immunofluorescence assay. Cell migration was assessed by "wound" healing and chemotactic migration assays. Cell invasion was assessed by a Matrigel-based invasion assay and in situ zymography. Matrix metalloproteinase 2 (MMP-2) and MMP-9 expression and secretion were examined by immunoblot analysis and an enzyme-linked immunosorbent assay, respectively. E-cadherin expression was assessed by flow cytometry, immunoblot analysis, and immunohistochemistry. Knockdown of E-cadherin was achieved by small interfering RNA. An experimental metastasis mouse model was created by intravenous injection of tumor cells; and lung tumor development in the mice was assessed by magnetic resonance imaging, gross observation, and histology.
  
  
  RESULTS
  SCC cellular morphology and actin organization were altered by 10 nM 1,25D(3) . 1,25D(3) inhibited SCC cell motility and invasion, which were associated with reduced expression and secretion of MMP-2 and MMP-9, and 1,25D(3) promoted the expression of E-cadherin. These findings were not observed in SCC-DR cells. Knock down of E-cadherin rescued 1,25D(3) -inhibited cell migration. Intravenous injection of SCC or SCC-DR cells resulted in the establishment of extensive pulmonary lesions in saline-treated C3H mice. Treatment with 1,25D(3) resulted in a marked reduction in the formation of lung tumor colonies in mice that were injected with SCC cells, but not in mice that were injected with SCC-DR cells.
  
  
  CONCLUSIONS
  1,25D(3) suppressed SCC cell motility, invasion, and metastasis, partially through the promotion of E-cadherin-mediated cell-cell adhesion.
authors: Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
authors: Yingyu
authors: Y
authors: Ma
authors: Wei-Dong
authors: WD
authors: Yu
authors: Bing
authors: B
authors: Su
authors: Mukund
authors: M
authors: Seshadri
authors: Wei
authors: W
authors: Luo
authors: Donald L
authors: DL
authors: Trump
authors: Candace S
authors: CS
authors: Johnson
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D048430:Cell Shape / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology* / Q000556:secondary; D051379:Mice; D008809:Mice, Inbred C3H; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009368:Neoplasm Transplantation
chemical_list: D015820:Cadherins; D002117:Calcitriol