Retinoic acid inhibits human melanoma tumor cell invasion.

Abstract:

:The anticancer effects of retinoids have been recognized both in vivo and in vitro; however, little is known about their mechanism of action. Our study evaluated the effects of retinoic acid on the invasiveness of four human melanoma cell lines in vitro and showed a time-dependent inhibition of the ability of these cells to penetrate matrigel-coated filters. The possible mechanisms of action responsible for the anti-invasive effect were further investigated, and the data showed that retinoic acid-treated cells: (a) secreted lower levels of collagenolytic enzymes detected in type IV collagen-containing polyacrylamide gels compared with control cells, which was demonstrated by a decreased ability to degrade [3H]proline-labeled type IV collagen substrate; (b) showed a reduction in PA activity, primarily in the form of tPA, as demonstrated by chromogenic analysis; (c) showed a heterogeneous response with regard to c-myc, c-fos and c-jun mRNA expression, as determined by Northern blot analysis; and (d) demonstrated a decrease in B-actin levels and an increase in vimentin, as demonstrated by Northern blot analysis and SDS-PAGE transblot analysis. Collectively, these data suggest that RA causes an inhibitory effect on tumor cell invasion through a reconstituted basement basement membrane matrix by suppressing type IV collagenolytic activity and PA activity, which is probably triggered through a complex series of oncogene trans-acting factors, ultimately affecting cytoskeletal expression.

journal_name

Anticancer Res

journal_title

Anticancer research

authors

Wood WR,Seftor EA,Lotan D,Nakajima M,Misiorowski RL,Seftor RE,Lotan R,Hendrix MJ

subject

Has Abstract

pub_date

1990-03-01 00:00:00

pages

423-32

issue

2A

eissn

0250-7005

issn

1791-7530

journal_volume

10

pub_type

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