MMP19 is upregulated during melanoma progression and increases invasion of melanoma cells

Abstract

During the progression of cutaneous melanomas, matrix metalloproteinases (MMPs) facilitate the tumour cells to traverse the basement membrane and invade the dermis. In this study, we analysed the expression of MMP19 in the course of melanoma progression. Although MMP19 was absent in melanocytes and melanoma cells of early stages of melanoma development, its expression was strongly upregulated in the neighbouring keratinocytes that may facilitate the vertical outgrowth of melanoma cells. In contrast to early stages, MMP19 was upregulated during the vertical growth phase of melanoma and in metastases. The upregulation of MMP19 in melanoma of Clark levels IV and V correlates with that of MMP2 and also simultaneously with ceased expression of E-cadherin. To reveal whether MMP19 facilitates the invasion of melanomas, we examined adhesion and migratory capacity of selected melanoma cell lines. Melanoma cell lines with low expression of MMP19 exhibited increased adhesion to various substrates and lower migration in comparison with the cell line with higher expression of MMP19. Moreover, ectopic expression of MMP19 could restore the migratory capacity of melanoma cells with low endogenous level of MMP19. These results suggest that the increase of MMP19 expression hallmarks the progression of cutaneous melanoma and might augment melanoma growth by promoting the invasion of tumour cells.

Catalytic activity of matrix metalloproteinase‐19 is essential for tumor suppressor and anti‐angiogenic activities in nasopharyngeal carcinoma

“…[38][39][40][41][42] The role of MMP19 in cancer is as controversial as for all other MMPs. MMP19 is up-regulated in astroglial tumor and melanoma 43,44 and reported to increase human keratinocyte cell proliferation, migration, and adhesion on type I collagen through the IGF-signaling pathway. 12 On the other hand, MMP19 is down-regulated or lost during neoplastic progression in breast, skin, and colon cancers.…”

Human matrix metalloproteinases: An ubiquitarian class of enzymes involved in several pathological processes

“…In particular, tumors from the central nervous system, such as glioma, display a diffuse MMP-19 expression which further correlates with an advanced state and invasiveness of the tumor (Brauer et al, 2011;Chan et al, 2011;Velinov et al, 2007). Nonetheless, MMP-19 quantification has become a WHO-accepted value for human glioma stadiation (Lettau et al, 2010;Müller et al, 2010;Stojic et al, 2008).…”

“…Association of MMP-19 with tumor aetiology is controversial as from divergent findings in animal models and in epidemiological studies. Only few aspects of its activity have been recently clarified (Brauer et al, 2011;Müller et al, 2010), and several aspects still remain obscure.…”

Oncogenic H-Ras Reprograms Madin-Darby Canine Kidney (MDCK) Cell-derived Exosomal Proteins Following Epithelial-Mesenchymal Transition

“…MMP-14 promotes cell invasion and motility by pericellular ECM degradation, shedding of CD44 (also detected in 21D1-Exos) and syndecan 1, and through activation of ERK (80). Expression of MMP-19 is associated with increased invasion, migratory behavior and early metastasis of melanoma cells (81), and localization of MMP-14 and -19 at the invasive tumor front is characteristic of highly motile invading tumor cells (81,82). The finding that MMP-14 and -19 are unique to 21D1-Exos and not observed in our previously published MDCK/21D1 secretome analysis (24), may represent a mechanism that allows exosome-bound proteases to traffic and function at distant/metastatic sites.…”