Document Detail

Regulation of motility, invasion, and metastatic potential of squamous cell carcinoma by 1α,25-dihydroxycholecalciferol.
MedLine Citation:
PMID:  22833444     Owner:  NLM     Status:  MEDLINE    
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.
Yingyu Ma; Wei-Dong Yu; Bing Su; Mukund Seshadri; Wei Luo; Donald L Trump; Candace S Johnson
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-07-25
Journal Detail:
Title:  Cancer     Volume:  119     ISSN:  1097-0142     ISO Abbreviation:  Cancer     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-23     Completed Date:  2013-03-21     Revised Date:  2014-09-12    
Medline Journal Info:
Nlm Unique ID:  0374236     Medline TA:  Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  563-74     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2012 American Cancer Society.
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MeSH Terms
Cadherins / genetics,  metabolism
Calcitriol / pharmacology*
Carcinoma, Squamous Cell / drug therapy,  pathology*
Cell Adhesion / drug effects,  genetics
Cell Line, Tumor
Cell Movement / drug effects*
Cell Shape / drug effects
Drug Evaluation, Preclinical
Gene Expression Regulation, Neoplastic / drug effects
Lung Neoplasms / drug therapy,  pathology*,  secondary
Mice, Inbred C3H
Neoplasm Invasiveness
Neoplasm Metastasis
Neoplasm Transplantation
Grant Support
CA067267/CA/NCI NIH HHS; CA085142/CA/NCI NIH HHS; CA095045/CA/NCI NIH HHS; P30CA16056/CA/NCI NIH HHS; R01 CA067267/CA/NCI NIH HHS; R01 CA067267-18/CA/NCI NIH HHS; R01 CA085142/CA/NCI NIH HHS; R01 CA085142-10/CA/NCI NIH HHS; R01 CA095045/CA/NCI NIH HHS; R01 CA095045-09/CA/NCI NIH HHS
Reg. No./Substance:
0/Cadherins; FXC9231JVH/Calcitriol

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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