<scp>MCAM</scp> Expression Facilitates Melanoma–Endothelial Interactions and Promotes Metastatic Disease Progression

Invasive growth and metastatic dissemination represent the primary cause of death in cancer patients. In order to successfully detach from the primary tumour and establish metastases in distant tissues, cancer cells need to dynamically rewire their cell adhesion machinery. Here we revisit the potential association of MCAM, a member of the immunoglobulin superfamily that was initially identified as a melanoma antigen, with disease progression. Using immunohistochemical stainings and bioinformatic analyses of published datasets, we find abundant MCAM expression both in primary and metastatic human melanomas. In additional bioinformatic analyses, we show that MCAM is highly expressed in foetal melanocytes and subsequently downregulated during melanocyte maturation. Bioinformatic inference of cellular communication networks reveals that melanoma cells with high MCAM expression more actively engage in signalling crosstalk with endothelial cells. Experimental investigations demonstrate that disruption of MCAM in melanoma cells inhibits their migration on endothelial cell surfaces in vitro and decreases their ability to develop spontaneous lung metastases in vivo. Taken together, our results could not confirm the notion that MCAM expression represents a useful biomarker for disease progression but provide evidence that MCAM expression might represent part of a reactivated embryonal transcriptional program that facilitates melanoma-endothelial cell interactions during metastatic progression.