Melanoma is the 5th most common tumor in females and the 6th in males and it is the tumour with the fastest rising incidence worldwide. Advanced melanomas are of concern because they represent 80% of skin-cancer related deaths (over 26000 deaths in 2020 in Europe alone) (Globocan 2020). The aggressiveness of this cancer type is reflected by the fact that that seemingly thin primary lesions (≥2 mm in depth) can already bear high risk of dissemination to lymph nodes that drain the tumour (sentinel lymph nodes) and ultimately, to distal sites. A series of treatments have been approved in the recent years, particularly involving immunotherapy. However, a significant fraction of these patients are or will become resistant. Therefore, a main unmet need in the field is a better understanding of the the first steps of the metastatic spread of melanoma.
Our group and others have demonstrated that melanoma cells act “at a distance”, preparing pre-metastatic niches before they colonized them. Soluble and vesicle-associated proteins secreted by malignant cells and/or their stroma have been proposed to facilitate tumor cell dissemination. We found that a key factor favouring these pre-metastatic sites is the growth factor Midkine (MDK). However, blockade of MDK reduced, but did not completely abrogate metastasis. Therefore, this proposal was set to identify other other long-range acting factors promoting metastasis in addition or in parallel to Midkine in the establishment of pre-metastatic niches.
