Therapeutic and Diagnostic Antibodies to CD146: Thirty Years of Research on Its Potential for Detection and Treatment of Tumors

CD146 (MCAM, MUC18, S-Endo1) is a transmembrane glycoprotein belonging to both CAM and mucin families. It exists as different splice variants and is cleaved from the membrane by metalloproteases to generate a soluble form. CD146 is expressed by numerous cancer cells as well as being one of the numerous proteins expressed by the vascular endothelium. It has also been identified on smooth muscle cells, pericytes, and some immune cells. This protein was initially described as an actor involved in tumor growth and metastatic dissemination processes. Some recent works highlighted the role of CD146 in angiogenesis. Interestingly, this knowledge allowed the development of therapeutic and diagnostic tools specifically targeting the different CD146 variants. The first antiCD146 antibody designed to study the function of this molecule, MUC18, was described by the Pr. J.P. Jonhson in 1987. In this review, we will discuss the 30 following years of research focused on the detection, study, and blocking of this protein in physiological and pathological processes.