High expression levels of collagenase-1 and stromelysin-1 correlate with shorter disease-free survival in human metastatic melanoma

Authors

  • Johanna Nikkola,

    1. Department of Oncology and Radiotherapy, Turku University Central Hospital, Turku, Finland
    2. MediCity Research Laboratory, University of Turku, Turku, Finland
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  • Pia Vihinen,

    Corresponding author
    1. Department of Oncology and Radiotherapy, Turku University Central Hospital, Turku, Finland
    2. MediCity Research Laboratory, University of Turku, Turku, Finland
    • MediCity Research Laboratory, University of Turku, Tykistökatu 6A, FIN-20520 Turku, Finland
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    • Fax: +358-2-333-7000

  • Tatyana Vlaykova,

    1. Department of Oncology and Radiotherapy, Turku University Central Hospital, Turku, Finland
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  • Marjo Hahka-Kemppinen,

    1. Department of Oncology, Helsinki University Central Hospital, Helsinki, Finland
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  • Veli-Matti Kähäri,

    1. Turku Centre for Biotechnology and Departments of Dermatology and Medical Biochemistry, Unviersity of Turkey, Turku, Finland
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  • Seppo Pyrhönen

    1. Department of Oncology and Radiotherapy, Turku University Central Hospital, Turku, Finland
    2. MediCity Research Laboratory, University of Turku, Turku, Finland
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Abstract

Matrix metalloproteinases (MMPs) are proteolytic enzymes capable of degrading extracellular matrix. Their role has been emphasized in tumor invasion, metastasis and tumor-induced angiogenesis. We studied the expression of collagenase-1 (MMP-1), stromelysin-1 (MMP-3) and collagenase-3 (MMP-13) in 70 melanoma metastases obtained from 56 patients treated with combined chemoimmunotherapy. The patients were divided into 2 groups using a cut-off point of 0% for MMP-1 expression and 20% for MMP-3 expression. We found that patients with MMP-1 positive metastases (n = 38) had significantly shorter disease-free survival compared to patients with MMP-1 negative metastases (n = 18) (median 11.2 vs. 17.0 months, p = 0.0383). The disease-free survival of patients with high levels of MMP-3 expression in their metastases (≥20% positive tumor cells, n = 14) was also significantly shorter compared to patients with lower levels of expression (n = 42) (median 5.1 vs. 14.0 months, p = 0.0294). The expression of MMP-13 did not correlate to survival parameters. We also found that the presence of melanin, a pigment produced by melanocytes, correlated with high expression levels of MMP-1 (p = 0.0002), MMP-3 (p < 0.0001) and MMP-13 (p = 0.0009). The high expression levels of MMP-13 were also associated with the presence of visceral metastases (p = 0.0284). Our findings suggest that MMP-1 and -3 may have a special role in melanoma metastasis formation and thus they could be used to measure the biological activity of the disease. © 2001 Wiley-Liss, Inc.

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