Retinoic acid inhibits human melanoma tumor cell invasion

W. R. Wood, E. A. Seftor, D. Lotan, M. Nakajima, R. L. Misiorowski, R. E.B. Seftor, R. Lotan, M. J.C. Hendrix*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

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 inhibitor effect on tumor cell invasion through a reconstituted 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.

Original languageEnglish (US)
Pages (from-to)423-432
Number of pages10
JournalAnticancer research
Volume10
Issue number2 A
StatePublished - 1990

Keywords

  • invasion
  • melanoma
  • retinoic acid

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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