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 MCAM gene.[5]
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| Aliases | MCAM, CD146, MUC18, melanoma cell adhesion molecule, HEMETCAM, MelCAM | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 155735; MGI: 1933966; HomoloGene: 4742; GeneCards: MCAM; OMA:MCAM - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Function
editMCAM functions as a receptor for laminin alpha 4,[6] a matrix molecule that is broadly expressed within the vascular wall. Accordingly, MCAM is highly expressed by cells that are components of the blood vessel wall, including vascular endothelial cells, smooth muscle cells and pericytes. 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.[7][8] CD146 T cells have been shown by Dagur and colleagues to produce IL-17.[9]
CD146 has been seen as a marker for mesenchymal stem cells isolated from multiple adult and fetal organs,[10] and its expression may be linked to multipotency; mesenchymal stem cells with greater differentiation potential express higher levels of CD146 on the cell surface.[11]
Relevance in cancer
editMCAM inhibits breast cancer progression.[12]
Normal melanocytes do not express MCAM and the expression of MCAM is first found in nevi and melanoma cells.[13] MCAM expression is positively correlated to melanoma progression at which the expression of MCAM is highest in metastatic melanoma cells. The significance of MCAM upregulation is evident in melanoma cells cultured in 3D skin reconstruct in which MCAM facilitates the migration of melanoma into the dermis. Without the expression of MCAM melanoma cells are controlled by keratinocytes in the epidermis that inhibit penetrance beyond the basement membrane. The control by keratinocytes are only achieved by E-cadherin expression on the surface of melanoma cells. Melanoma cells with functional E-cadherin on the surface can only exclusively grow in the epidermis as keratinocytes frequently downregulate the expression of MCAM on melanoma cells.[13]
References
edit- ^ a b c GRCh38: Ensembl release 89: ENSG00000076706 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000032135 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Kuske MD, Johnson JP (1999). "Assignment of the human melanoma cell adhesion molecule gene (MCAM) to chromosome 11 band q23.3 by radiation hybrid mapping". Cytogenetics and Cell Genetics. 87 (3–4): 258. doi:10.1159/000015439. PMID 10702685. S2CID 37508075.
- ^ Flanagan K, Fitzgerald K, Baker J, Regnstrom K, Gardai S, Bard F, et al. (2012). "Laminin-411 is a vascular ligand for MCAM and facilitates TH17 cell entry into the CNS". PLOS ONE. 7 (7): e40443. Bibcode:2012PLoSO...740443F. doi:10.1371/journal.pone.0040443. PMC 3391262. PMID 22792325.
- ^ 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". Blood. 106 (8): 2923–4. doi:10.1182/blood-2005-06-2307. PMID 16204154.
- ^ Elshal MF, Khan SS, Raghavachari N, Takahashi Y, Barb J, Bailey JJ, et al. (November 2007). "A unique population of effector memory lymphocytes identified by CD146 having a distinct immunophenotypic and genomic profile". BMC Immunology. 8: 29. doi:10.1186/1471-2172-8-29. PMC 2248207. PMID 17999761.
- ^ Dagur PK, Biancotto A, Wei L, Sen HN, Yao M, Strober W, et al. (December 2011). "MCAM-expressing CD4(+) T cells in peripheral blood secrete IL-17A and are significantly elevated in inflammatory autoimmune diseases". Journal of Autoimmunity. 37 (4): 319–27. doi:10.1016/j.jaut.2011.09.003. PMC 3223259. PMID 21959269.
- ^ Covas DT, Panepucci RA, Fontes AM, Silva WA, Orellana MD, Freitas MC, et al. (May 2008). "Multipotent mesenchymal stromal cells obtained from diverse human tissues share functional properties and gene-expression profile with CD146+ perivascular cells and fibroblasts". Experimental Hematology. 36 (5): 642–54. doi:10.1016/j.exphem.2007.12.015. PMID 18295964.
- ^ 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 Cells. 28 (4): 788–98. doi:10.1002/stem.312. PMID 20127798. S2CID 45009922.
- ^ Ouhtit A, Gaur RL, Abd Elmageed ZY, Fernando A, Thouta R, Trappey AK, et al. (April 2009). "Towards understanding the mode of action of the multifaceted cell adhesion receptor CD146". Biochimica et Biophysica Acta (BBA) - Reviews on Cancer. 1795 (2): 130–6. doi:10.1016/j.bbcan.2009.01.002. PMID 19356677.
- ^ a b Haass NK, Smalley KS, Li L, Herlyn M (June 2005). "Adhesion, migration and communication in melanocytes and melanoma". Pigment Cell Research. 18 (3): 150–9. doi:10.1111/j.1600-0749.2005.00235.x. PMID 15892711.
Further reading
edit- Wang Z, Xu Q, Zhang N, Du X, Xu G, Yan X (August 2020). "CD146, from a melanoma cell adhesion molecule to a signaling receptor". Signal Transduction and Targeted Therapy. 5 (1): 148. doi:10.1038/s41392-020-00259-8. PMC 7421905. PMID 32782280.
- Guezguez B, Vigneron P, Lamerant N, Kieda C, Jaffredo T, Dunon D (November 2007). "Dual role of melanoma cell adhesion molecule (MCAM)/CD146 in lymphocyte endothelium interaction: MCAM/CD146 promotes rolling via microvilli induction in lymphocyte and is an endothelial adhesion receptor". Journal of Immunology. 179 (10): 6673–85. doi:10.4049/jimmunol.179.10.6673. PMID 17982057.
- Shih IM (September 1999). "The role of CD146 (Mel-CAM) in biology and pathology". The Journal of Pathology. 189 (1): 4–11. doi:10.1002/(SICI)1096-9896(199909)189:1<4::AID-PATH332>3.0.CO;2-P. PMID 10451481. S2CID 43326956.
- Staquicini FI, Tandle A, Libutti SK, Sun J, Zigler M, Bar-Eli M, et al. (October 2008). "A subset of host B lymphocytes controls melanoma metastasis through a melanoma cell adhesion molecule/MUC18-dependent interaction: evidence from mice and humans". Cancer Research. 68 (20): 8419–28. doi:10.1158/0008-5472.CAN-08-1242. PMC 2718575. PMID 18922915.
- Johnson JP, Rothbächer U, Sers C (October 1993). "The progression associated antigen MUC18: a unique member of the immunoglobulin supergene family". Melanoma Research. 3 (5): 337–40. doi:10.1097/00008390-199310000-00006. PMID 8292890. S2CID 43280514.
- McGary EC, Lev DC, Bar-Eli M (2002). "Cellular adhesion pathways and metastatic potential of human melanoma". Cancer Biology & Therapy. 1 (5): 459–65. doi:10.4161/cbt.1.5.158. PMID 12496470.
- Barbe L, Lundberg E, Oksvold P, Stenius A, Lewin E, Björling E, et al. (March 2008). "Toward a confocal subcellular atlas of the human proteome". Molecular & Cellular Proteomics. 7 (3): 499–508. doi:10.1074/mcp.M700325-MCP200. PMID 18029348.
- Wang N, Fan Y, Ni P, Wang F, Gao X, Xue Q, Tang L (2008). "High glucose effect on the role of CD146 in human proximal tubular epithelial cells in vitro". Journal of Nephrology. 21 (6): 931–40. PMID 19034879.
- Bidlingmaier S, He J, Wang Y, An F, Feng J, Barbone D, et al. (February 2009). "Identification of MCAM/CD146 as the target antigen of a human monoclonal antibody that recognizes both epithelioid and sarcomatoid types of mesothelioma". Cancer Research. 69 (4): 1570–7. doi:10.1158/0008-5472.CAN-08-1363. PMC 2752656. PMID 19221091.
- 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 Cells. 28 (4): 788–98. doi:10.1002/stem.312. PMID 20127798. S2CID 45009922.
- Tripodo C, Di Bernardo A, Ternullo MP, Guarnotta C, Porcasi R, Ingrao S, et al. (January 2009). "CD146(+) bone marrow osteoprogenitors increase in the advanced stages of primary myelofibrosis". Haematologica. 94 (1): 127–30. doi:10.3324/haematol.13598. PMC 2625423. PMID 19029148.
- Samuels TL, Handler E, Syring ML, Pajewski NM, Blumin JH, Kerschner JE, Johnston N (September 2008). "Mucin gene expression in human laryngeal epithelia: effect of laryngopharyngeal reflux". The Annals of Otology, Rhinology, and Laryngology. 117 (9): 688–95. doi:10.1177/000348940811700911. PMID 18834073. S2CID 23385606.
- Bardin N, Blot-Chabaud M, Despoix N, Kebir A, Harhouri K, Arsanto JP, et al. (May 2009). "CD146 and its soluble form regulate monocyte transendothelial migration". Arteriosclerosis, Thrombosis, and Vascular Biology. 29 (5): 746–53. doi:10.1161/ATVBAHA.108.183251. PMID 19229070.
- Fritzsche FR, Wassermann K, Rabien A, Schicktanz H, Dankof A, Loening SA, et al. (August 2008). "CD146 protein in prostate cancer: revisited with two different antibodies". Pathology. 40 (5): 457–64. doi:10.1080/00313020802197996. PMID 18604730. S2CID 205448423.
- Melnikova VO, Balasubramanian K, Villares GJ, Dobroff AS, Zigler M, Wang H, et al. (October 2009). "Crosstalk between protease-activated receptor 1 and platelet-activating factor receptor regulates melanoma cell adhesion molecule (MCAM/MUC18) expression and melanoma metastasis". The Journal of Biological Chemistry. 284 (42): 28845–55. doi:10.1074/jbc.M109.042150. PMC 2781430. PMID 19703903.
- Chen W, Zhang HL, Jiang YG, Li JH, Liu BL, Sun MY (February 2009). "Inhibition of CD146 gene expression via RNA interference reduces in vitro perineural invasion on ACC-M cell". Journal of Oral Pathology & Medicine. 38 (2): 198–205. doi:10.1111/j.1600-0714.2008.00706.x. PMID 19200179.
- Zabouo G, Imbert AM, Jacquemier J, Finetti P, Moreau T, Esterni B, et al. (2009). "CD146 expression is associated with a poor prognosis in human breast tumors and with enhanced motility in breast cancer cell lines". Breast Cancer Research. 11 (1): R1. doi:10.1186/bcr2215. PMC 2687703. PMID 19123925.
- Schwab KE, Gargett CE (November 2007). "Co-expression of two perivascular cell markers isolates mesenchymal stem-like cells from human endometrium". Human Reproduction. 22 (11): 2903–11. doi:10.1093/humrep/dem265. PMID 17872908.
- Malyszko J, Malyszko JS, Kozminski P, Pawlak K, Mysliwiec M (July 2008). "Adipokines, linking adipocytes and vascular function in hemodialyzed patients, may also be possibly related to CD146, a novel adhesion molecule". Clinical and Applied Thrombosis/Hemostasis. 14 (3): 338–45. doi:10.1177/1076029607305083. PMID 18160586. S2CID 43210730.
- Zheng C, Qiu Y, Zeng Q, Zhang Y, Lu D, Yang D, et al. (November 2009). "Endothelial CD146 is required for in vitro tumor-induced angiogenesis: the role of a disulfide bond in signaling and dimerization". The International Journal of Biochemistry & Cell Biology. 41 (11): 2163–72. doi:10.1016/j.biocel.2009.03.014. PMID 19782948.
- Saito O, Saito T, Okuda K, Okuda K, Kotoda A, Akimoto T, et al. (February 2008). "Serum adiponectin and markers of endothelial injury in hemodialysis patients with arteriosclerosis obliterans". Clinical and Experimental Nephrology. 12 (1): 58–64. doi:10.1007/s10157-007-0012-7. PMID 18175063. S2CID 34180131.
External links
edit- CD146+Antigen at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Human MCAM genome location and MCAM gene details page in the UCSC Genome Browser.