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

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 (> or = 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.

• Authors: Johanna Nikkola, Pia Vihinen, Tatyana Vlaykova, Marjo Hahka-Kemppinen, Veli-Matti Kähäri, Seppo Pyrhönen
• Journal: International journal of cancer (Int J Cancer) Vol. 97 Issue 4 Pg. 432-8 (Feb 01 2002) ISSN: 0020-7136 [Print] United States
• PMID: 11802203 (Publication Type: Clinical Trial, Clinical Trial, Phase II, Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2001 Wiley-Liss, Inc.

Chemical References

• Immunologic Factors
• Interferon-alpha
• Interleukin-2
• Melanins
• Neoplasm Proteins
• Bleomycin
• Vincristine
• Lomustine
• Dacarbazine
• Collagenases
• collagenase 1
• Matrix Metalloproteinase 3

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, therapeutic use)
• Bleomycin (administration & dosage)
• Cell Division
• Collagenases (biosynthesis, genetics)
• Combined Modality Therapy
• Dacarbazine (administration & dosage)
• Disease-Free Survival
• Enzyme Induction
• Female
• Humans
• Immunologic Factors (therapeutic use)
• Immunotherapy
• Interferon-alpha (therapeutic use)
• Interleukin-2 (therapeutic use)
• Lomustine (administration & dosage)
• Male
• Matrix Metalloproteinase 3 (biosynthesis, genetics)
• Melanins (analysis)
• Melanocytes (enzymology)
• Melanoma (blood supply, drug therapy, enzymology, mortality, secondary, therapy)
• Middle Aged
• Neoplasm Proteins (biosynthesis, genetics)
• Neoplastic Stem Cells (enzymology)
• Prognosis
• Radiotherapy, Adjuvant
• Vincristine (administration & dosage)