The influence of 1,25-dihydroxyvitamin D3 and 1,24-dihydroxyvitamin D3 on alphavbeta3 integrin expression in cancer cell lines.
Integrins are cell-surface receptors engaged in important cancer invasion processes, such as adhesion, migration, proliferation and differentiation. The aim of this study was to evaluate the effect of 1,25-dihydroxyvitamin D3 (calcitriol) and its metabolite 1,24-dihydroxyvitamin D3 (PRI-2191) on alphavbeta3 integrin expression in various cancer cell lines. The expression levels of the beta3 and alphav integrins were reduced only in the WEHI-3 and LLC cell lines by the two compounds. Calcitriol or PRI-2191 treatment caused differentiation of WEHI-3 mouse leukemia cells, but apoptosis of LLC cells. WEHI-3 and LLC cells exposed to calcitriol or PRI-2191 lost their migratory and adhesive potentials. The inhibition of migratory potential was higher in the LLC cells than in the WEHI-3 cells and appeared to correlate with the increased down-regulation of alphavbeta3 integrin by calcitriol or PRI-2191. The observed in vivo effects (antitumor and antimetastatic) in mice bearing subcutaneously transplanted LLC cancer are possibly associated with inhibited migratory potential as a consequence of the lowered integrin expression caused by calcitriol or PRI-2191.
Wietrzyk
Joanna
J
Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Wroclaw, Poland. wietrzyk@iitd.pan.wroc.pl
Filip
Beata
B
Milczarek
Magdalena
M
Klopotowska
Dagmara
D
Maciejewska
Magdalena
M
Dabrowska
Krystyna
K
Kurzepa
Aneta
A
Dzimira
Stanislaw
S
Madej
Janusz
J
Kutner
Andrzej
A
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002117:Calcitriol / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004100:Dihydroxycholecalciferols / Q000494:pharmacology*; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000032:analysis*; D009361:Neoplasm Invasiveness
D000970:Antineoplastic Agents; D004100:Dihydroxycholecalciferols; D039302:Integrin alphaVbeta3; C023850:1 alpha,24-dihydroxyvitamin D3; D002117:Calcitriol