These results have been deepened by using two antibodies generated in rat. CD146 variants. The first anti-CD146 antibody designed to study the function of this molecule, MUC18, was explained 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. Keywords: cancer, CD146, antibody, therapy, diagnosis 1. Introduction Cluster of differentiation 146 (CD146) also named melanoma cell associated molecule (MCAM)/Mucin 18 (MUC18)/S-Endo 1 was first discovered in metastatic melanoma and its expression was rapidly associated to a poor prognosis. Since this initial discovery, CD146 was found to be upregulated in many malignancy types. Thereafter, CD146 was also recognized on endothelial cells where it is involved in angiogenesis. Angiogenesis, which corresponds to the formation of new blood vessels from pre-existing vessels, largely contributes to tumor development. The identification of new proteins and cells involved in the development and dissemination of tumors remains an important challenge to generate diagnostic and therapeutic tools. For several decades, studies have highlighted CD146 as a key actor of tumor growth and angiogenesis. CD146 displays 5-Iodotubercidin different isoforms and could thus constitute a novel therapeutic target. Many studies describe structural features, localization, and functions of CD146 in the vascular endothelium and tumor cells. The timeline of research on CD146 is usually presented in Physique 1. Open in a separate window Physique 1 Timeline of research on CD146. This timeline represents the principal discoveries (in green) and antibodies (in blue) related to CD146 [1,2,3,4,5,6,7,8,9,10,11,12,13,14]. This review will now focus on the role of the different isoforms of CD146 with a particular desire 5-Iodotubercidin for the diagnostic and therapeutic tools targeting the molecule. 2. Description and Cellular Localization of CD146 2.1. Genomic Description of CD146 The CD146 gene is located specifically around the arm q23.3 of chromosome 11 in humans and on chromosome 9 in mice. The gene encoding the CD146 protein extends over 5-Iodotubercidin 14kb. CD146 structure is composed of five immunoglobulin-like domains, two variable domains of V2 type, and three constant domains of C2 type, but also a transmembrane domain name and an intracytoplasmic portion [15]. The extracellular part of the molecule, including the five immunoglobulin domains, is usually encoded by 13 exons. The transmembrane and intracellular domains are encoded by three exons. The promoter of CD146 presents different putative binding sites and motifs including AP1, AP-2, cAMP Response Element (CRE), SP1, CArG, and c-myb. Analysis of this DNA segments suggests that the four SP-1 sites, the two AP-2 domains, and one response element to Adenosine MonoPhosphate cyclic (AMPc)-(CRE) form the minimal promotor of CD146 [16]. Specific sites play a role in CD146 expression. The AP-2 sites which are located at ?131 and ?302 by relative to the initial ATG, reduced promoter activity by 70% and 44%, respectively [16]. Moreover, when mutated, the CRE site inhibits by 70% the transcription of the gene. Therefore, AP-2 [17] and CRE sites [18] have been explained to modulate CD146 expression in melanoma cells, leading to an increase in tumor growth and metastatic potential in these cancers. In fact, the AP-2 binding site located in the promoter (located at ?23 bp) is an inhibitor of the transcription of CD146 while the other AP-2 sites (located respectively at ?131, ?302, and ?505) are transcription activators [16,17]. The CD146 mRNA has been first recognized in human melanoma malignancy cells Fgf2 and represents 3.3 Kb [19]. Its encoding region is about 1940 bp. There exists a strong homology between the human and mouse mRNA sequences, but several differences can be noted. In humans, there 5-Iodotubercidin is a lengthening of the 3 and 5 Untranslated Transcribed Region (5 UTR) region as wells as a loss of 6pb in exon 2. The encoding regions and 5UTR region have a homology of about 80% and 72%, respectively, between the murine and human genes and there is only 31% of homology for the 3UTR region. Finally, the protein sequence has about 76% homology.