The role of EGFR and matrix metalloproteinases in malignant melanoma progression

Principal Investigator: Professor Gordana Zamolo

Department: Department of Pathology, Faculty of Medicine

Institution: University of Rijeka, Croatia


Key words: EGFR, metaloproteinases, melanoma of the skin

The most significant risk factor for melanoma development is exposure to UV radiation, and it was estimated that 65 % of melanoma occur as a direct result of UV radiation. Most common clinically significant mutation which is present in 40% of melanoma is V600E BRAF. It activates the MAPK / ERK signaling pathway, thus stimulating the survival and proliferation of melanoma cells. Epidermal growth factor receptor (EGFR) is often over- expressed protein in multiple tumors. It is also identified as a target molecule for molecular targeted therapy. Matrix metaloproteinases ( MMPs ) are zinc-dependent endopeptidases capable of degrading matrix proteins and processing of bioactive molecules that play an important role in cell proliferation, migration, angiogenesis and cell apoptosis. Many tumors, including the melanoma of the skin, base on autocrine activation mechanism and are partly independent of exogenous growth factors . The study of Meierjohann et al. in 2010 has shown that MMP - 13 acts as a mediator of proliferation of melanocytes and melanoma cells . Research by Gong , et al. from 2008, in turn demonstrated that inhibition of MMP - 2 blocked the phosphorylation of EGFR , which contributes to metastatic spread of tumors , while research Kim MK , et al . from 2013 shows the association of UV damaged DNA and the transcriptional activation of MMP - 1 in human skin in vivo. The principle of matrix metalloproteinases expression in melanoma is still unexplored , however, FGF ( UB Hoffmann et al . 2005) or BRAFV600E ( Huntington JT et al . 2004) autocrine signaling pathways might be responsible for their expression in some cell lines of melanoma.
Our hypothesis is that BRAF V600E positive melanomas and melanomas exposed to UV light ( sun-exposed melanomas ) will demonstrate increased protein expression of matrix metalloproteinases and EGFR. Increased protein expression of these biomarkers can affect tumor progression and decreased survival of patients. This research will determine the justification of the use of matrix metalloproteinase inhibitors in the treatment of melanoma.