Matrix metalloproteinase-12 expression is increased in cutaneous melanoma and associated with tumor aggressiveness

Abstract

Cutaneous melanoma is the most malignant form of skin cancer characterized by aggressive invasion. Matrix metalloproteinases play essential roles in tumor invasion due to their ECM degrading capacity. However, the clinical significance of matrix metalloproteinasis (MMP)-12 in human cutaneous melanoma has not been addressed yet. In the present study, we investigated MMP-12 expression level in 298 patients with cutaneous melanoma and 60 normal skin tissue specimens by immunohistochemistry assay. Appropriate statistical analysis was utilized to determine the association of MMP-12 with clinical features and prognosis of melanoma. Results showed that MMP-12 expression was increased in cutaneous melanoma compared with that in normal skin. It was also found that MMP-12 expression in melanoma was significantly associated with tumor invasion and metastasis. Univariate survival analysis indicated that patients with melanoma of high MMP-12 expression had unfavorable overall survival compared with those of low MMP-12 expression. Cox's proportional hazards analysis showed that MMP-12 expression was an independent prognostic marker of overall survival for patients with cutaneous melanoma. These results proved that MMP-12 expression was increased in cutaneous melanoma and associated with tumor progression. It also provided the first evidence that MMP-12 level could be an independent prognostic marker for patients with cutaneous melanoma.

Genetic variants in the metzincin metallopeptidase family genes predict melanoma survival

“…Metzincins are considered key molecules in degradation of the extracellular matrix and play an important role in a variety of biological processes and pathological disorders, such as asthma, rheumatoid arthritis, and cancer, including CM. The alterations of the metzincin metallopeptidase family genes in CM development and progression have been previously reported …”

“…The alterations of the metzincin metallopeptidase family genes in CM development and progression have been previously reported. [18][19][20][21] In the present study, we performed survival analysis for genetic variants in 75 metzincin metallopeptidase family genes and CMSS using the available MDACC and Harvard GWAS datasets. Four independent representative SNPs (MMP16 rs10090371 C>A, ADAMTS3 rs788935 T>C, TLL2 rs10882807 T>C, and MMP9 rs3918251 A>G) were identified as predictors of CMSS.…”

“…For example, matrix metalloproteinase 9 ( MMP9 ) has been reported to be associated with cancer invasiveness and metastasis, and inhibitors against MMP9 represent a promising strategy for anti‐melanoma therapy . MMP12 expression has been reported to be increased in CM and related to tumor invasion and metastasis . Moreover, high expression of the disintegrin and metalloproteinase domain‐containing protein 10 ( ADAM10 ) was found to be related to melanoma metastasis .…”

“…18 MMP12 expression has been reported to be increased in CM and related to tumor invasion and metastasis. 19 Moreover, high expression of the disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) was found to be related to melanoma metastasis. 20 The disintegrin-metalloproteinases with thrombospondin domains (ADAMTS) genes have been suggested to act as tumor suppressors in various cancers, including melanoma, and ADAMTS18 mutations can promote cell growth, migration, and metastasis of melanoma.…”

Biomarkers in Malignant Melanoma: Recent Trends and Critical Perspective

“…macrophage metalloelastase) was also found to be increased in cutaneous melanoma compared to normal skin and was significantly associated with invasion and metastasis. Furthermore, patients with high MMP-12 level had unfavorable overall survival (31). Finally, increased MMP-23 (EC 3.4.24.-) expression in primary melanomas is inversely associated with the presence of tumor infiltrating lymphocytes, suggesting a role for tumor-derived MMP-23 in the suppression of antitumor immune responses (32).…”