CD146 (cluster of differentiation 146) also known as the melanoma cell adhesion molecule (MCAM) or cell surface glycoprotein MUC18, is a 113kDa cell adhesion molecule currently used as a marker for endothelial cell lineage. In humans, the CD146 protein is encoded by the MCAMgene.
Its function is still poorly understood, but evidence points to it being part of the endothelial junction associated with the actin cytoskeleton. A member of the Immunoglobulin superfamily, it consists of five Ig domains, a transmembrane domain, and a cytoplasmic region. It is expressed on chicken embryonic spleen and thymus, activated human T cells, endothelial progenitors such as angioblasts and mesenchymal stem cells, and strongly expressed on blood vessel endothelium and smooth muscle.
Two isoforms exist (MCAM long (MCAM-1), and MCAM short, or MCAM-s) which differ in the length of their cytoplasmic domain. Activation of these isoforms seems to produce functional differences as well. Natural killer cells transfected with MCAM-1 demonstrate decreased rolling velocity and increased cell adhesion to an endothelial cell monolayer and increased microvilli formation while cells transfected with MCAM-s showed no change in adhesion characteristics. Since these characteristics are important in leukocyte extravasation, MCAM-1 may be an important part of the inflammatory response.
CD146 has been demonstrated to appear on a small subset of T and B lymphocytes in the peripheral blood of healthy individuals. The CD146+ T cells display an immunophenotype consistent with effector memory cells and have a distinct gene profile from the CD146- T cells.CD146 T cells have been shown by Dagur and colleagues to produce IL-17.
CD146 has been seen as a marker for mesenchymal stem cells isolated from multiple adult and fetal organs, and its expression may be linked to multipotency; mesenchymal stem cells with greater differentiation potential express higher levels of CD146 on the cell surface.
^Elshal MF, Khan SS, Takahashi Y, Solomon MA, McCoy JP (October 2005). "CD146 (Mel-CAM), an adhesion marker of endothelial cells, is a novel marker of lymphocyte subset activation in normal peripheral blood". Blood106 (8): 2923–4. doi:10.1182/blood-2005-06-2307. PMID16204154.
^Dagur PK, Biancotto A, Wei L, Sen HN, Yao M, Strober W, Nussenblatt RB, and McCoy JP; J Autoimmunity, 2011, doi: 10.1016/j.jaut.2011.09.003
^Covas DT, Panepucci RA, Fontes AM, Silva WA, Orellana MD, Freitas MC, Neder L, Santos AR, Peres LC, Jamur MC, Zago MA (May 2008). "Multipotent mesenchymal stromal cells obtained from diverse human tissues share functional properties and gene-expression profile with CD146+ perivascular cells and fibroblasts". Exp. Hematol.36 (5): 642–54. doi:10.1016/j.exphem.2007.12.015. PMID18295964.
^Russell KC, Phinney DG, Lacey MR, Barrilleaux BL, Meyertholen KE, O'Connor KC (April 2010). "In vitro high-capacity assay to quantify the clonal heterogeneity in trilineage potential of mesenchymal stem cells reveals a complex hierarchy of lineage commitment". Stem Cells28 (4): 788–98. doi:10.1002/stem.312. PMID20127798.
^Ouhtit A, Gaur RL, Abd Elmageed ZY, Fernando A, Thouta R, Trappey AK, Abdraboh ME, El-Sayyad HI, Rao P, Raj MG (April 2009). "Towards understanding the mode of action of the multifaceted cell adhesion receptor CD146". Biochim. Biophys. Acta1795 (2): 130–6. doi:10.1016/j.bbcan.2009.01.002. PMID19356677.
Russell KC, Phinney DG, Lacey MR, et al. (2010). "In vitro high-capacity assay to quantify the clonal heterogeneity in trilineage potential of mesenchymal stem cells reveals a complex hierarchy of lineage commitment". Stem Cells28 (4): 788–98. doi:10.1002/stem.312. PMID20127798.
Samuels TL, Handler E, Syring ML, et al. (2008). "Mucin gene expression in human laryngeal epithelia: effect of laryngopharyngeal reflux". Ann. Otol. Rhinol. Laryngol.117 (9): 688–95. PMID18834073.
Bardin N, Blot-Chabaud M, Despoix N, et al. (2009). "CD146 and its soluble form regulate monocyte transendothelial migration". Arterioscler. Thromb. Vasc. Biol.29 (5): 746–53. doi:10.1161/ATVBAHA.108.183251. PMID19229070.
Schwab KE, Gargett CE (2007). "Co-expression of two perivascular cell markers isolates mesenchymal stem-like cells from human endometrium". Hum. Reprod.22 (11): 2903–11. doi:10.1093/humrep/dem265. PMID17872908.
Malyszko J, Malyszko JS, Kozminski P, et al. (2008). "Adipokines, linking adipocytes and vascular function in hemodialyzed patients, may also be possibly related to CD146, a novel adhesion molecule". Clin. Appl. Thromb. Hemost.14 (3): 338–45. doi:10.1177/1076029607305083. PMID18160586.
Zheng C, Qiu Y, Zeng Q, et al. (2009). "Endothelial CD146 is required for in vitro tumor-induced angiogenesis: the role of a disulfide bond in signaling and dimerization". Int. J. Biochem. Cell Biol.41 (11): 2163–72. doi:10.1016/j.biocel.2009.03.014. PMID19782948.
Saito O, Saito T, Okuda K, et al. (2008). "Serum adiponectin and markers of endothelial injury in hemodialysis patients with arteriosclerosis obliterans". Clin. Exp. Nephrol.12 (1): 58–64. doi:10.1007/s10157-007-0012-7. PMID18175063.