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Membrane-type 1 matrix metalloproteinase-mediated progelatinase A activation in non-tumorigenic and tumorigenic humaneratinocytes
Elevated expression of type IV collagenases (MMP-2 and MMP-9) has been strongly correlated with tumour progression and metastasis in various tumours. Here, we analysed expression and activation of these MMPs in non-tumourigenic HaCaT cells and the malignant HaCaT variant II-4 (rt). In monolayer cult...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2000
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2408778/ https://www.ncbi.nlm.nih.gov/pubmed/11044366 http://dx.doi.org/10.1054/bjoc.2000.1454 |
Sumario: | Elevated expression of type IV collagenases (MMP-2 and MMP-9) has been strongly correlated with tumour progression and metastasis in various tumours. Here, we analysed expression and activation of these MMPs in non-tumourigenic HaCaT cells and the malignant HaCaT variant II-4 (rt). In monolayer cultures, both cell types secreted latent MMP-2 (proMMP-2) in comparable amounts, while MMP-9 production was clearly higher in II-4 (rt) cells. Upon contact with fibrillar collagen type I the malignant II-4 (rt) cells, but not the HaCaT cells, gained the capability to activate proMMP-2. This process is shown to be membrane-associated and mediated by MT1-MMP. Surprisingly, all membrane preparations from either HaCaT cells or II-4 (rt) cells grown as monolayers, as well as within collagen gels, contained considerable amounts of active MT1-MMP. However, within collagen gels HaCaT cells showed significantly higher TIMP-2 levels compared to II-4 (rt) cells. This indicates that TIMP-2 might play a central role for MT1-MMP-mediated gelatinolytic activity. Indeed, collagen type I-induced MT1-MMP-mediated proMMP-2 activation by II-4 (rt) membranes could be completely abolished by an excess of TIMP-2. In conclusion, our data suggest that MT1-MMP-mediated proMMP-2 activation might be associated with malignant progression of epidermal tumour cells. © 2000 Cancer Research Campaign |
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