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
| Autor: | M J, Hendrix, W R, Wood, E A, Seftor, D, Lotan, M, Nakajima, R L, Misiorowski, R E, Seftor, W G, Stetler-Stevenson, S J, Bevacqua, L A, Liotta |
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| Rok vydání: | 1990 |
| Předmět: |
Dose-Response Relationship
Drug Receptors Cell Surface Tretinoin Basement Membrane Receptors Laminin Plasminogen Activators Microbial Collagenase Enzyme Induction Cell Adhesion Tumor Cells Cultured Humans Neoplasm Invasiveness RNA Messenger Neoplasm Metastasis Receptors Immunologic Melanoma Cell Division |
| Zdroj: | Cancer research. 50(13) |
| ISSN: | 0008-5472 |
| Popis: | Treatment of four A375 human melanoma sublines (A375, A375P, A375P-5, A375M), exhibiting distinct metastatic potentials in vivo, with beta-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 Mr 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 Na2(51)CrO4-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 (f) 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. |
| Databáze: | OpenAIRE |
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