CD146

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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

  1. ↑ 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.
  2. ↑ 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. PMC 3391262. PMID 22792325.
  3. ↑ 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.
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ 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.
  8. ↑ 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

External links

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