Retinoic Acid Inhibition of Human Melanoma Cell Invasion through a Reconstituted Basement Membrane and Its Relation to Decreases in the Expression of Proteolytic Enzymes and Motility Factor Receptor

Mary J.C. Hendrix, W. Rebecca Wood, Elisabeth A. Seftor, Richard E.B. Seftor, Ronald L. Misiorowski, Sandra J. Bevacqua, Dafna Lotan, Motowo Nakajima, Reuben Lotan, William G. Stetler-Stevenson, Lance A. Liotta, Mark E. Sobel, Avraham Raz

Research output: Contribution to journalArticle

139 Scopus citations

Abstract

Treatment of four A375 human melanoma sublines (A375, A375P, A375P-5, A375M), exhibiting distinct metastatic potentials in viVo, with β-all-trans-retinoic acid in vitro caused a dose- and time-dependent inhibition of the ability of these cells to penetrate Matrigel-coated filters using a reconstituted basement membrane invasion assay. The possible mechanisms of action responsible for the antiinvasive effect were further investigated, and the data showed that compared with untreated cells the retinoic acid-treated cells: (a) secreted lower levels of collagenolytic enzymes, as demonstrated by a decreased ability of the cells to degrade [3H]proline-labeled type IV collagen substrate and by a reduction in the activity of a secreted MT 64,000 collagenolytic enzyme detected in type IV collagen-containing Polyacrylamide gels; (b) expressed lower levels of the human type IV collagenase mRNA (except in the A375P cells), as detected by Northern blot analysis; (c) exhibited decreased levels of tissue plasminogen activator activity, as demonstrated by a chromogenic assay; (d) were 10–40% less adhesive to a reconstituted basement membrane matrix, as determined by a 60-min Na251Cr04-labeled cell attachment assay; (e) exhibited an increase in the high affinity metastasis-associated cell surface laminin receptor, as determined by flow cytometry after binding of fluorescently labeled laminin receptor antibody; and (/) expressed decreased amounts of gp78, a cell surface receptor for motility factor, demonstrated by immunoblotting and immunofluorescence. Collectively, these data suggest that retinoic acid inhibits tumor cell invasion through a basement membrane-like matrix by suppressing matrix degradation and by altering cell surface receptors.

Original languageEnglish (US)
Pages (from-to)4121-4130
Number of pages10
JournalCancer Research
Volume50
Issue number13
StatePublished - Jul 1 1990

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Retinoic Acid Inhibition of Human Melanoma Cell Invasion through a Reconstituted Basement Membrane and Its Relation to Decreases in the Expression of Proteolytic Enzymes and Motility Factor Receptor'. Together they form a unique fingerprint.

  • Cite this

    Hendrix, M. J. C., Wood, W. R., Seftor, E. A., Seftor, R. E. B., Misiorowski, R. L., Bevacqua, S. J., Lotan, D., Nakajima, M., Lotan, R., Stetler-Stevenson, W. G., Liotta, L. A., Sobel, M. E., & Raz, A. (1990). Retinoic Acid Inhibition of Human Melanoma Cell Invasion through a Reconstituted Basement Membrane and Its Relation to Decreases in the Expression of Proteolytic Enzymes and Motility Factor Receptor. Cancer Research, 50(13), 4121-4130.