Adhesion receptors, signalling and cellular migration: the role of HLA-DR molecules in melanoma cells.

Melanoma, is one of the most aggressive cancers worldwide, its incidence rates increase rapidly in western population and unfortunately it is responsible of about 20% overall cancer mortality as well as of approximately 80% skin cancer related mortality. The aggressive metastatic trend of melanoma is associated to the improved expression of adhesion receptors as well as to the deregulation of their functions that promote both the tumour cells detachment from primary tumour and the interaction between tumour cells and cellular blood components. In this contest, the aim of our work was to understand the consequences on melanoma metastatic progression and migration of the Major Histocompatibility Complex (MHC) class II mediated signalling. Indeed, the MHC class II molecules are signalling receptors whose engagement leads to the activation of several signalling pathways by tyrosine and serine/threonine kinases phosphorylation. The constitutive MHC class II expression is restricted to professional APCs, nevertheless almost 50% of melanomas express constitutively the MHC class II molecules. In two MHC class II constitutive expressing melanoma cell lines we showed that the HLA-DR mediated signalling increases the expression of adhesion receptors and ILK and the expression and activation of FAK, PAX, AKT, ERK and PKC signalling proteins. Notably, the HLA-DR mediated signalling increases also the melanoma cell migrations through micro pore filters coated with extracellular matrix proteins and through Boyden chambers with differential media compartmentalization. Therefore, our results suggest that the HLA-DR mediated signalling plays a new role to promote melanoma progression regulating cell adhesion, motility and metastatic dissemination.