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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...
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Formato: | Texto |
Lenguaje: | English |
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Nature Publishing Group
2000
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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 |
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author | Baumann, P Zigrino, P Mauch, C Breitkreutz, D Nischt, R |
author_facet | Baumann, P Zigrino, P Mauch, C Breitkreutz, D Nischt, R |
author_sort | Baumann, P |
collection | PubMed |
description | 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 |
format | Text |
id | pubmed-2408778 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2000 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-24087782009-09-10 Membrane-type 1 matrix metalloproteinase-mediated progelatinase A activation in non-tumorigenic and tumorigenic humaneratinocytes Baumann, P Zigrino, P Mauch, C Breitkreutz, D Nischt, R Br J Cancer Regular Article 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 Nature Publishing Group 2000-11 2000-10-26 /pmc/articles/PMC2408778/ /pubmed/11044366 http://dx.doi.org/10.1054/bjoc.2000.1454 Text en Copyright © 2000 Cancer Research Campaign https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Regular Article Baumann, P Zigrino, P Mauch, C Breitkreutz, D Nischt, R Membrane-type 1 matrix metalloproteinase-mediated progelatinase A activation in non-tumorigenic and tumorigenic humaneratinocytes |
title | Membrane-type 1 matrix metalloproteinase-mediated progelatinase A activation in non-tumorigenic and tumorigenic humaneratinocytes |
title_full | Membrane-type 1 matrix metalloproteinase-mediated progelatinase A activation in non-tumorigenic and tumorigenic humaneratinocytes |
title_fullStr | Membrane-type 1 matrix metalloproteinase-mediated progelatinase A activation in non-tumorigenic and tumorigenic humaneratinocytes |
title_full_unstemmed | Membrane-type 1 matrix metalloproteinase-mediated progelatinase A activation in non-tumorigenic and tumorigenic humaneratinocytes |
title_short | Membrane-type 1 matrix metalloproteinase-mediated progelatinase A activation in non-tumorigenic and tumorigenic humaneratinocytes |
title_sort | membrane-type 1 matrix metalloproteinase-mediated progelatinase a activation in non-tumorigenic and tumorigenic humaneratinocytes |
topic | Regular Article |
url | 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 |
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