Biology:CD99

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Short description: Protein-coding gene in humans


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

CD99 antigen (Cluster of differentiation 99), also known as MIC2 or single-chain type-1 glycoprotein, is a heavily O-glycosylated transmembrane protein that is encoded by the CD99 gene in humans.[1][2][3] The protein has a mass of 32 kD. Unusually for a gene present on the X chromosome, the CD99 gene does not undergo X inactivation, and it was the first such pseudoautosomal gene to be discovered in humans.[4]

Expression

It is expressed on all leukocytes but highest on thymocytes[5][6][7] and is believed to augment T-cell adhesion[8][9] and apoptosis of double positive T cells.[10] It has been found in endothelial cells and in the periodontium, including gingival fibroblasts and gingival epithelial cells.[3] It also participates in migration and activation.[11] There is also experimental evidence that it binds to cyclophilin A.[12]

It is found on the cell surface of Ewing's sarcoma tumors [13] and is positive in granulosa cell tumors.[14] It is more expressed in malignant gliomas than in the brain, and such overexpression results in higher levels of invasiveness and lower rates of survival.[15] Antibodies to CD99 are used in diagnostic immunohistochemistry to distinguish Ewing's sarcoma from other tumours of similar histological appearance, as well as for the identification of thymic tumours, and of spindle cell tumours, such as synovial sarcoma, haemangiopericytoma, and meningioma.[4] EWS/FLI is thought to regulate CD99, but knockdown of EWS/FLI results in only a modest reduction in CD99. When CD99 expression is knocked down in human cells with Ewing's sarcoma and those cells are grafted onto mice, tumor and bone metastasis development is reduced.[13]

Reducing CD99 expression results in higher β-III tubulin expression and more neurite outgrowth.[13]

Upregulating CD99 expression in the cell line L428, a Hodgkin's lymphoma line, resulted in those cells redifferentiating towards B cells. Consequently, the loss of B-cell differentiation in Hodgkin's lymphoma may be due to CD99 downregulation.[16]

Men appear to express higher levels of CD99 than women.[17]

Prognostic Value

In patients with diffuse large B-cell lymphoma (DLBCL) with the germinal center B-cell (GCB, classified according to the Muris algorithm) subtype, positive expression of CD99 resulted in better 2-year event free survival (EFS) and 2-year overall survival (OS) compared to negative expression of CD99. In patients with DLBCL with non-GCB, however, negative expression of CD99 resulted in better 2-year EFS and 2-year OS.[18] In patients with non-small cell lung cancer (NSCLC), higher CD99 expression in the stroma results in better prognosis.[19]

Interactions

There is evidence that through suppressing β1 integrin affinity, CD99 inhibits cell-extracellular matrix adhesion.[20]

References

  1. ↑ "Entrez Gene: CD99 CD99 molecule". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4267. 
  2. ↑ "Genetic evidence that a Y-linked gene in man is homologous to a gene on the X chromosome". Nature 302 (5906): 346–9. 1983. doi:10.1038/302346a0. PMID 6188056. Bibcode: 1983Natur.302..346G. 
  3. ↑ 3.0 3.1 "CD99 ligation induces intercellular cell adhesion molecule-1 expression and secretion in human gingival fibroblasts". Arch. Oral Biol. 58 (1): 82–93. January 2013. doi:10.1016/j.archoralbio.2012.06.011. PMID 22795566. 
  4. ↑ 4.0 4.1 Manual of Diagnostic Cytology (2nd ed.). Greenwich Medical Media, Ltd.. 2003. pp. 145–146. ISBN 978-1-84110-100-2. 
  5. ↑ "Monoclonal antibodies directed against the E2 protein (MIC2 gene product) induce exposure of phosphatidylserine at the thymocyte cell surface". Biochemistry 32 (38): 10096–101. September 1993. doi:10.1021/bi00089a027. PMID 8399135. 
  6. ↑ "Flow cytometric assessment of human MIC2 expression in bone marrow, thymus, and peripheral blood". Blood 83 (2): 415–25. January 1994. doi:10.1182/blood.V83.2.415.415. PMID 7506950. 
  7. ↑ "Engagement of CD99 induces up-regulation of TCR and MHC class I and II molecules on the surface of human thymocytes". Journal of Immunology 161 (2): 749–54. July 1998. doi:10.4049/jimmunol.161.2.749. PMID 9670951. http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=9670951. 
  8. ↑ "CD99 (E2) up-regulates alpha4beta1-dependent T cell adhesion to inflamed vascular endothelium under flow conditions". European Journal of Immunology 30 (10): 3061–5. October 2000. doi:10.1002/1521-4141(200010)30:10<3061::AID-IMMU3061>3.0.CO;2-M. PMID 11069091. 
  9. ↑ "CD99 monoclonal antibody induce homotypic adhesion of Jurkat cells through protein tyrosine kinase and protein kinase C-dependent pathway". Immunology Letters 71 (1): 33–41. January 2000. doi:10.1016/S0165-2478(99)00165-0. PMID 10709783. 
  10. ↑ "Apoptosis of immature thymocytes mediated by E2/CD99". Journal of Immunology 158 (6): 2543–50. March 1997. doi:10.4049/jimmunol.158.6.2543. PMID 9058785. 
  11. ↑ "CD99 activates T cells via a costimulatory function that promotes raft association of TCR complex and tyrosine phosphorylation of TCR zeta". Experimental & Molecular Medicine 39 (2): 176–84. April 2007. doi:10.1038/emm.2007.20. PMID 17464179. 
  12. ↑ "Identification of cyclophilin A as a CD99-binding protein by yeast two-hybrid screening". Immunology Letters 95 (2): 155–9. September 2004. doi:10.1016/j.imlet.2004.07.001. PMID 15388255. 
  13. ↑ 13.0 13.1 13.2 "CD99 inhibits neural differentiation of human Ewing sarcoma cells and thereby contributes to oncogenesis". J. Clin. Invest. 120 (3): 668–80. March 2010. doi:10.1172/JCI36667. PMID 20197622. 
  14. ↑ "CD99". NordiQC. http://www.nordiqc.org/Run-12/Assessment/assessment-CD99.htm. 
  15. ↑ "Overexpression of CD99 Increases the Migration and Invasiveness of Human Malignant Glioma Cells". Genes Cancer 3 (9–10): 535–49. September 2012. doi:10.1177/1947601912473603. PMID 23486730. 
  16. ↑ "[CD99 regulates redifferentiation of classical Hodgkin's lymphoma cell line L428 towards B cells]" (in zh). Nan Fang Yi Ke da Xue Xue Bao 33 (2): 235–8. February 2013. PMID 23443779. 
  17. ↑ "Sex differences in inflammatory cytokines and CD99 expression following in vitro lipopolysaccharide stimulation". Shock 38 (1): 37–42. July 2012. doi:10.1097/SHK.0b013e3182571e46. PMID 22575993. 
  18. ↑ "CD99 expression and newly diagnosed diffuse large B-cell lymphoma treated with rituximab-CHOP immunochemotherapy". Ann. Hematol. 91 (12): 1897–906. December 2012. doi:10.1007/s00277-012-1533-z. PMID 22864685. 
  19. ↑ "CD99 is a novel prognostic stromal marker in non-small cell lung cancer". Int. J. Cancer 131 (10): 2264–73. November 2012. doi:10.1002/ijc.27518. PMID 22392539. 
  20. ↑ "The activation of CD99 inhibits cell-extracellular matrix adhesion by suppressing β(1) integrin affinity". BMB Rep 45 (3): 159–64. March 2012. doi:10.5483/BMBRep.2012.45.3.159. PMID 22449702. 

Further reading

External links



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