High expression levels of collagenase-1 and stromelysin-1 correlate with shorter disease-free survival in human metastatic melanoma.
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.
Nikkola
Johanna
J
Department of Oncology and Radiotherapy, Turku University Central Hospital, Turku, Finland.
Vihinen
Pia
P
Vlaykova
Tatyana
T
Hahka-Kemppinen
Marjo
M
Kähäri
Veli-Matti
VM
Pyrhönen
Seppo
S
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000627:therapeutic use; D001761:Bleomycin / Q000008:administration & dosage; D002455:Cell Division; D017364:Collagenases / Q000096:biosynthesis* / Q000235:genetics; D003131:Combined Modality Therapy; D003606:Dacarbazine / Q000008:administration & dosage; D018572:Disease-Free Survival; D004790:Enzyme Induction; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D007167:Immunotherapy; D016898:Interferon-alpha / Q000627:therapeutic use; D007376:Interleukin-2 / Q000627:therapeutic use; D008130:Lomustine / Q000008:administration & dosage; D008297:Male; D019278:Matrix Metalloproteinase 3 / Q000096:biosynthesis* / Q000235:genetics; D008543:Melanins / Q000032:analysis; D008544:Melanocytes / Q000201:enzymology; D008545:Melanoma / Q000098:blood supply / Q000188:drug therapy / Q000201:enzymology / Q000401:mortality / Q000556:secondary* / Q000628:therapy; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000201:enzymology; D011379:Prognosis; D018714:Radiotherapy, Adjuvant; D014750:Vincristine / Q000008:administration & dosage
D007155:Immunologic Factors; D016898:Interferon-alpha; D007376:Interleukin-2; D008543:Melanins; D009363:Neoplasm Proteins; D001761:Bleomycin; D014750:Vincristine; D008130:Lomustine; D003606:Dacarbazine; D017364:Collagenases; C417249:collagenase 1; D019278:Matrix Metalloproteinase 3