Effects of 1,25-dihydroxyvitamin D3 on tumor cell invasion to the extracellular matrix in human fibrosarcoma HT1080 cells and its correlation with laminin.
We investigated the role of the active form of vitamin D, 1,25-dihydroxyvitamin D3[1,25(OH)2D3], in promoting tumor cell invasiveness through the extracellular matrix, and showed that 1,25(OH)2D3-induced reduction of laminin production by the cells was correlated with the inhibitory effect of the hormone on tumor cell invasiveness. 1,25(OH)2D3 significantly inhibited invasiveness through the matrix, type IV collagenolytic and migratory activity, but not cell attachment to the matrix in human fibrosarcoma HT1080 cells. The 1,25(OH)2D3-induced inhibition showed the same dose dependency and magnitude for invasiveness as for the effects on type IV collagenolysis and cell migration. 1,25(OH)2D3 inhibited laminin production from the cells in a dose-dependent manner. The inhibitory effects of 1,25(OH)2D3 on the invasiveness, type IV collagenolysis and cell migration appeared to parallel the hormone-induced reduction of laminin production. Antilaminin monoclonal antibody, blocking the activity of laminin in the culture medium, inhibited HT1080 cell invasiveness. In the presence of exogenous laminin, 1,25(OH)2D3-induced inhibition of invasion was not observed. These findings suggest that 1,25(OH)2D3 acts on HT1080 cells, inhibiting the expression of laminin from the cells, and that the reduced laminin expression leads to the inhibition in the type IV collagenolytic and migratory activity of the cells, and consequently, to the inhibition of invasiveness through the extracellular matrix.
Yudoh
K
K
Department of Orthopaedic Surgery, Toyama Medical and Pharmaceutical University, Japan.
Matsui
H
H
Tsuji
H
H
D002117:Calcitriol / Q000494:pharmacology*; D002465:Cell Movement; D004273:DNA, Neoplasm / Q000096:biosynthesis; D005109:Extracellular Matrix / Q000473:pathology*; D005354:Fibrosarcoma / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D007797:Laminin / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000032:analysis; D018167:Receptors, Calcitriol / Q000032:analysis; D014407:Tumor Cells, Cultured
D004273:DNA, Neoplasm; D007797:Laminin; D012333:RNA, Messenger; D018167:Receptors, Calcitriol; D002117:Calcitriol