INTACT VITRONECTIN INDUCES MATRIX METALLOPROTEINASE-2 AND TISSUE INHIBITOR OF METALLOPROTEINASES-2 EXPRESSION AND ENHANCED CELLULAR INVASION BY MELANOMA-CELLS

Citation
Lm. Bafetti et al., INTACT VITRONECTIN INDUCES MATRIX METALLOPROTEINASE-2 AND TISSUE INHIBITOR OF METALLOPROTEINASES-2 EXPRESSION AND ENHANCED CELLULAR INVASION BY MELANOMA-CELLS, The Journal of biological chemistry, 273(1), 1998, pp. 143-149
Citations number
40
Categorie Soggetti
Biology
ISSN journal
00219258
Volume
273
Issue
1
Year of publication
1998
Pages
143 - 149
Database
ISI
SICI code
0021-9258(1998)273:1<143:IVIMMA>2.0.ZU;2-C
Abstract
The initial site of melanoma cell metastasis is frequently the regiona l lymph nodes, and the appearance of lymph node metastasis correlates with poor prognosis, Lymph node adhesion is mediated by an interaction between the tumor cell integrin alpha v beta 3 and lymph node vitrone ctin. In this study, we explored the relationship between adhesion and proteolysis by examining the direct effect of vitronectin receptor li gation on matrix metalloproteinase-2 (MMP-2) production by B16F1 and B 16F10 melanoma cells. We report a dose-dependent increase in secretion of both MMP-2 and tissue inhibitor of metalloproteinases-2 (TIMP-2) i n response to vitronectin. Cellular invasiveness was also enhanced by vitronectin, as shown by the increased ability of vitronectin-treated cells to invade a synthetic basement membrane (Matrigel). Both the vit ronectin-induced MMP-2 production and vitronectin-enhanced invasion we re blocked by the peptide ligand Arg-Gly-Asp-Ser (RGDS). Furthermore, neither plasmin-degraded vitronectin nor the peptide ligand RGDS stimu lated MMP-2 secretion or invasiveness, indicating that a multivalent l igand-receptor interaction rather than simple receptor occupancy was r equired for MMP-2 induction. MMP-2 and MMP-2/TIMP-2 interaction with t he plasma membrane of melanoma cells resulted in enhanced catalytic ac tivity against C-14-labeled gelatin, suggesting that membrane associat ion may function in posttranslational regulation of MMP-2 activity, Th is is supported by data showing increased cellular invasion by cells c ontaining membrane-bound MMP-2. Binding of proMMP-2 and proMMP-2/TIMP- 2 to melanoma cells was not inhibited by RGDS, and melanoma cell adhes ion to vitronectin was unaffected by pro-or active MMP-2, indicating t hat MMP-2 did not interact with the murine vitronectin receptor, Toget her, these data provide evidence for a functional link between adhesio n and proteolysis and suggest a potential mechanism whereby adhesion o f an invasive cell to the extracellular matrix regulates subsequent in vasive behavior.