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Molecular Cancer
Published in: Molecular Cancer 1/2010

Open Access 01-12-2010 | Research

MMP13 mediates cell cycle progression in melanocytes and melanoma cells: in vitro studies of migration and proliferation

Authors: Svenja Meierjohann, Anita Hufnagel, Elisabeth Wende, Markus A Kleinschmidt, Katarina Wolf, Peter Friedl, Stefan Gaubatz, Manfred Schartl

Published in: Molecular Cancer | Issue 1/2010

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Abstract

Background

Melanoma cells are usually characterized by a strong proliferative potential and efficient invasive migration. Among the multiple molecular changes that are recorded during progression of this disease, aberrant activation of receptor tyrosine kinases (RTK) is often observed. Activation of matrix metalloproteases goes along with RTK activation and usually enhances RTK-driven migration. The purpose of this study was to examine RTK-driven three-dimensional migration of melanocytes and the pro-tumorigenic role of matrix metalloproteases for melanocytes and melanoma cells.

Results

Using experimental melanocyte dedifferentiation as a model for early melanomagenesis we show that an activated EGF receptor variant potentiates migration through three-dimensional fibrillar collagen. EGFR stimulation also resulted in a strong induction of matrix metalloproteases in a MAPK-dependent manner. However, neither MAPK nor MMP activity were required for migration, as the cells migrated in an entirely amoeboid mode. Instead, MMPs fulfilled a function in cell cycle regulation, as their inhibition resulted in strong growth inhibition of melanocytes. The same effect was observed in the human melanoma cell line A375 after stimulation with FCS. Using sh- and siRNA techniques, we could show that MMP13 is the protease responsible for this effect. Along with decreased proliferation, knockdown of MMP13 strongly enhanced pigmentation of melanocytes.

Conclusions

Our data show for the first time that growth stimuli are mediated via MMP13 in melanocytes and melanoma, suggesting an autocrine MMP13-driven loop. Given that MMP13-specific inhibitors are already developed, these results support the evaluation of these inhibitors in the treatment of melanoma.
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Metadata
Title
MMP13 mediates cell cycle progression in melanocytes and melanoma cells: in vitro studies of migration and proliferation
Authors
Svenja Meierjohann
Anita Hufnagel
Elisabeth Wende
Markus A Kleinschmidt
Katarina Wolf
Peter Friedl
Stefan Gaubatz
Manfred Schartl
Publication date
01-12-2010
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2010
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-9-201

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