CD146
| Melanoma cell adhesion molecule | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||||||
| Symbols | MCAM ; CD146; MUC18 | ||||||||||||
| External IDs | OMIM: 155735 MGI: 1933966 HomoloGene: 4742 GeneCards: MCAM Gene | ||||||||||||
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| Orthologs | |||||||||||||
| Species | Human | Mouse | |||||||||||
| Entrez | 4162 | 84004 | |||||||||||
| Ensembl | ENSG00000076706 | ENSMUSG00000032135 | |||||||||||
| UniProt | P43121 | Q8R2Y2 | |||||||||||
| RefSeq (mRNA) | NM_006500 | NM_023061 | |||||||||||
| RefSeq (protein) | NP_006491 | NP_075548 | |||||||||||
| Location (UCSC) |
Chr 11: 119.31 – 119.32 Mb |
Chr 9: 44.13 – 44.14 Mb | |||||||||||
| PubMed search | |||||||||||||
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.[1]
Function
MCAM functions as a receptor for laminin alpha 4,[2] 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.[3][4] CD146 T cells have been shown by Dagur and colleagues to produce IL-17.[5]
CD146 has been seen as a marker for mesenchymal stem cells isolated from multiple adult and fetal organs,[6] and its expression may be linked to multipotency; mesenchymal stem cells with greater differentiation potential express higher levels of CD146 on the cell surface.[7]
Clinical significance
MCAM inhibits breast cancer progression.[8]
References
- ↑ 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". Cytogenet. Cell Genet. 87 (3–4): 258. doi:10.1159/000015439. PMID 10702685.
- ↑ Flanagan K, Fitzgerald K, Baker J, Regnstrom K, Gardai S, Bard F, Mocci S, Seto P, You M, Larochelle C, Prat A, Chow S, Li L, Vandevert C, Zago W, Lorenzana C, Nishioka C, Hoffman J, Botelho R, Willits C, Tanaka K, Johnston J, Yednock T (2012). "Laminin-411 Is a Vascular Ligand for MCAM and Facilitates TH17 Cell Entry into the CNS". PLOS ONE 7 (7): e40443. doi:10.1371/journal.pone.0040443.
- ↑ 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, Munson PJ, Solomon MA, Danner RL, McCoy JP (2007). "A unique population of effector memory lymphocytes identified by CD146 having a distinct immunophenotypic and genomic profile". BMC Immunol. 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, Nussenblatt RB, McCoy JP (2011). "MCAM-expressing CD4(+) T cells in peripheral blood secrete IL-17A and are significantly elevated in inflammatory autoimmune diseases". J. Autoimmun. 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, 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. 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.
- ↑ 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. Acta 1795 (2): 130–6. doi:10.1016/j.bbcan.2009.01.002. PMID 19356677.
Further reading
- 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". J. Immunol. 179 (10): 6673–85. doi:10.4049/jimmunol.179.10.6673. PMID 17982057.
- Shih IM (1999). "The role of CD146 (Mel-CAM) in biology and pathology". J. Pathol. 189 (1): 4–11. doi:10.1002/(SICI)1096-9896(199909)189:1<4::AID-PATH332>3.0.CO;2-P. PMID 10451481.
- Staquicini FI, Tandle A, Libutti SK, Sun J, Zigler M, Bar-Eli M, Aliperti F, Pérez EC, Gershenwald JE, Mariano M, Pasqualini R, Arap W, Lopes JD (2008). "A Subset of Host B-Lymphocytes Control Melanoma Metastasis Through a MCAM/MUC18-dependent Interaction: Evidence from Mice and Humans". Cancer Res. 68 (20): 8419–28. doi:10.1158/0008-5472.CAN-08-1242. PMC 2718575. PMID 18922915.
- Johnson JP, Rothbächer U, Sers C (1993). "The progression associated antigen MUC18: a unique member of the immunoglobulin supergene family". Melanoma Res. 3 (5): 337–40. doi:10.1097/00008390-199310000-00006. PMID 8292890.
- McGary EC, Lev DC, Bar-Eli M (2002). "Cellular adhesion pathways and metastatic potential of human melanoma". Cancer Biol. Ther. 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, Asplund A, Pontén F, Brismar H, Uhlén M, Andersson-Svahn H (2008). "Toward a confocal subcellular atlas of the human proteome". Mol. Cell 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". J. Nephrol. 21 (6): 931–40. PMID 19034879.
- Bidlingmaier S, He J, Wang Y, An F, Feng J, Barbone D, Gao D, Franc B, Broaddus VC, Liu B (2009). "Identification of MCAM/CD146 as the target antigen of a human monoclonal antibody that recognizes both epithelioid and sarcomatoid types of mesothelioma". Cancer Res. 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 (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.
- Tripodo C, Di Bernardo A, Ternullo MP, Guarnotta C, Porcasi R, Ingrao S, Gianelli U, Boveri E, Iannitto E, Franco G, Florena AM (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 (2008). "Mucin gene expression in human laryngeal epithelia: effect of laryngopharyngeal reflux". Ann. Otol. Rhinol. Laryngol. 117 (9): 688–95. doi:10.1177/000348940811700911. PMID 18834073.
- Bardin N, Blot-Chabaud M, Despoix N, Kebir A, Harhouri K, Arsanto JP, Espinosa L, Perrin P, Robert S, Vely F, Sabatier F, Le Bivic A, Kaplanski G, Sampol J, Dignat-George F (2009). "CD146 and its soluble form regulate monocyte transendothelial migration". Arterioscler. Thromb. Vasc. Biol. 29 (5): 746–53. doi:10.1161/ATVBAHA.108.183251. PMID 19229070.
- Fritzsche FR, Wassermann K, Rabien A, Schicktanz H, Dankof A, Loening SA, Dietel M, Jung K, Kristiansen G (2008). "CD146 protein in prostate cancer: revisited with two different antibodies". Pathology 40 (5): 457–64. doi:10.1080/00313020802197996. PMID 18604730.
- Melnikova VO, Balasubramanian K, Villares GJ, Dobroff AS, Zigler M, Wang H, Petersson F, Price JE, Schroit A, Prieto VG, Hung MC, Bar-Eli M (2009). "Crosstalk between Protease-activated Receptor 1 and Platelet-activating Factor Receptor Regulates Melanoma Cell Adhesion Molecule (MCAM/MUC18) Expression and Melanoma Metastasis". J. Biol. Chem. 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 (2009). "Inhibition of CD146 gene expression via RNA interference reduces in vitro perineural invasion on ACC-M cell". J. Oral Pathol. Med. 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, Birnbaum D, Bertucci F, Chabannon C (2009). "CD146 expression is associated with a poor prognosis in human breast tumors and with enhanced motility in breast cancer cell lines". Breast Cancer Res. 11 (1): R1. doi:10.1186/bcr2215. PMC 2687703. PMID 19123925.
- 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. PMID 17872908.
- Malyszko J, Malyszko JS, Kozminski P, Pawlak K, Mysliwiec M (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. PMID 18160586.
- Zheng C, Qiu Y, Zeng Q, Zhang Y, Lu D, Yang D, Feng J, Yan X (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. PMID 19782948.
- Saito O, Saito T, Okuda K, Okuda K, Kotoda A, Akimoto T, Ando Y, Muto S, Ishikawa SE, Kusano E (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. PMID 18175063.
External links
- CD146 Antigen at the US National Library of Medicine Medical Subject Headings (MeSH)
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