MMP1, MMP9, MMP11 and MMP13 in melanoma and its metastasis - key points in understanding the mechanisms and celerity of tumor dissemination.

Abstract

Matrix metalloproteinase (MMP)1, MMP9, MMP11, and MMP13 are overexpressed in malignant melanoma (MM), being associated with tumor invasive phase, metastases, and more aggressive neoplastic phenotypes. The main objective of the current study was to correlate the expression of the MMPs with the evolution of MM toward distant metastasis. We designed a retrospective cohort study, including 13 patients with metastatic MM. Data concerning age, sex, localization of the primary lesion and metastasis, and histological and immunohistochemical features (intensity of expression and percent of positive cells for MMPs) were statistically processed. The time between the diagnosis of primitive melanoma and the diagnosis of metastasis ranged between 0 and 73 months, with a mean value of 18.3 months. The metastases rich in MMP1- and MMP9-positive cells occurred earlier than the metastases with low levels of positive cells. The mean period until metastasis was shorter for the MMP1-expressing tumors than the ones without MMP1 expression. MMP13 expression in the tumor and its metastasis was significantly linked with the time until the metastasis occurrence. This study emphasizes the roles of MMP1, MMP9, and MMP13 in the process of metastasis in melanoma and the opportunity to use them as therapeutic targets and surveillance molecules.