Browsing by Author "Salomies, Lotta"

Cutaneous melanoma is a malignant tumor originating from pigment cells in the skin. The incidence of melanoma has been on an increasing trend for several decades, and while survival rates have improved in recent years, the mortality of metastasized melanoma continues to be extremely high. Thus, identifying aggressive melanoma cases as early as possible is crucial. Matrix metalloproteinases (MMPs) are a group of proteins that break down the extracellular matrix and play important roles in processes such as embryonic development and cancer dissemination. In particular, the membrane-bound MMP14 protein is known to have a fundamental role in the metastasis of many cancer types. Furthermore, the expression of MMP16 protein has recently been demonstrated to be correlated with poor prognosis in melanoma patients. In this thesis I studied MMP14 and MMP16 in the context of melanoma with two approaches: 1) I examined these proteins in clinical samples of patients with metastasized melanoma and assessed whether the expression level of either MMP14 or MMP16 showed correlation with patient survival time or the dissemination of the disease. 2) I attempted to use RNA interference to generate melanoma cells with loss of MMP14 or MMP16 expression, for later use in assessing the effect of the silencing on the cells’ capacity to form metastases. In the thesis I discovered that high expression of MMP16 already in the primary melanoma tumor correlates with the later development of brain and other distant metastases. These results suggest that MMP16 could potentially be used as a tool to help identify aggressive melanomas and define the prognosis of melanoma patients already at early stages of the diagnosis. Whereas the silencing of MMP14 expression in melanoma cells was successful, I could not reliably validate the loss of MMP16 expression at protein level despite multiple efforts. This may in part be explained by the complex protein-level regulation of MMP16, leading to difficulties when using antibody-based methods to assess its expression.