Knockdown of L1CAM significantly reduces metastasis in a xenograft model of human melanoma: L1CAM is a potential target for anti-melanoma therapy

Abstract

Malignant melanoma is a malignant neoplasia of the skin, which spreads aggressively. After distant metastases had formed almost no chance for cure exists. Thus, it is extremely important to identify druggable targets with different modes of action to enable individualised therapy even after distant metastases have formed and to prevent the formation of further metastases. Different proteins are already known to be promising targets for therapeutic agents because of their metastases promoting potential. One of these proteins, which need to be researched closely, is the surface protein L1 cell adhaesion molecule (L1CAM). In this work, we investigated the impact of a knockdown of L1CAM protein expression on the ability of malignant melanoma cells to metastasize in in vitro models reflecting part of the metastatic cascade and in vivo in a xenograft model. We chose two different cell lines: MeWo and MV3. It is known that MeWo wild type cells expressed considerably more L1CAM than wildtype MV3 cells. The in vitro experiments showed no distinct difference in cellular behaviour reflecting metastasis formation between cells with or wildtype cells without L1CAM knockdown. In vivo however there was a significant reduction in the number of spontaneous metastases into the mouse lungs within both groups of L1CAM knockdown cells. The impact was measurable in both cell lines, in the initially high L1CAM expressing MeWo cells, but also in the initially low L1CAM expressing MV3 cells. In both cell lines an influence of L1CAM expression on the expression of other genes which modulate epithelial mesenchymal transition or those which suppress melanoma growth such as p53 and p21 were noted. The significant impact of L1CAM expression on the process of metastasis formation of melanoma cells was shown, which makes L1CAM an interesting novel therapeutic target.