| Citation: |
ZHAO Qian, LI Feng. Role and Research Progress of CD81 in Tumors[J]. Cancer Research on Prevention and Treatment, 2025, 52(3): 233-240. DOI: 10.3971/j.issn.1000-8578.2025.24.0730
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This article elaborates on the structure and function of CD81, explores its role and value in malignant solid and hematological tumors, introduces CD81-related antibodies and small-molecule compounds, analyzes the advantages and challenges faced by anti-CD81 therapy in clinical applications, and looks forward to the future application prospects of anti-CD81 therapy in the treatment of malignant hematological diseases.
Competing interests: The authors declare that they have no competing interests.
| [1] |
Becic A, Leifeld J, Shaukat J, et al. Tetraspanins as Potential Modulators of Glutamatergic Synaptic Function[J]. Front Mol Neurosci, 2022, 14: 801882. doi: 10.3389/fnmol.2021.801882
|
| [2] |
New C, Lee ZY, Tan KS, et al. Tetraspanins: Host Factors in Viral Infections[J]. Int J Mol Sci, 2021, 22(21): 11609. doi: 10.3390/ijms222111609
|
| [3] |
Karam J, Méresse S, Kremer L, et al. The roles of tetraspanins in bacterial infections[J]. Cell Microbiol, 2020, 22(12): e13260.
|
| [4] |
Bailly C, Thuru X. Targeting of Tetraspanin CD81 with Monoclonal Antibodies and Small Molecules to Combat Cancers and Viral Diseases[J]. Cancers (Basel), 2023, 15(7): 2186. doi: 10.3390/cancers15072186
|
| [5] |
Oren R, Takahashi S, Doss C, et al. TAPA-1, the target of an antiproliferative antibody, defines a new family of transmembrane proteins[J]. Mol Cell Biol, 1990, 10(8): 4007-4015.
|
| [6] |
Zimmerman B, Kelly B, McMillan BJ, et al. Crystal Structure of a Full-Length Human Tetraspanin Reveals a Cholesterol-Binding Pocket[J]. Cell, 2016, 167(4): 1041-1051. e11.
|
| [7] |
Seigneuret M, Delaguillaumie A, Lagaudrière-Gesbert C, et al. Structure of the tetraspanin main extracellular domain. A partially conserved fold with a structurally variable domain insertion[J]. J Biol Chem, 2001, 276(43): 40055-40064. doi: 10.1074/jbc.M105557200
|
| [8] |
Seigneuret M. Complete predicted three-dimensional structure of the facilitator transmembrane protein and hepatitis C virus receptor CD81: conserved and variable structural domains in the tetraspanin superfamily[J]. Biophys J, 2006, 90(1): 212-227. doi: 10.1529/biophysj.105.069666
|
| [9] |
Kitadokoro K, Ponassi M, Galli G, et al. Subunit association and conformational flexibility in the head subdomain of human CD81 large extracellular loop[J]. Biol Chem, 2002, 383(9): 1447-1452.
|
| [10] |
Kitadokoro K, Bordo D, Galli G, et al. CD81 extracellular domain 3D structure: insight into the tetraspanin superfamily structural motifs[J]. EMBO J, 2001, 20(1-2): 12-18.
|
| [11] |
van Deventer SJ, Dunlock VE, van Spriel AB. Molecular interactions shaping the tetraspanin web[J]. Biochem Soc Trans, 2017, 45(3): 741-750. doi: 10.1042/BST20160284
|
| [12] |
Palor M, Stejskal L, Mandal P, et al. Cholesterol sensing by CD81 is important for hepatitis C virus entry[J]. J Biol Chem, 2020, 295(50): 16931-16948. doi: 10.1074/jbc.RA120.014761
|
| [13] |
Yang Y, Liu XR, Greenberg ZJ, et al. Open conformation of tetraspanins shapes interaction partner networks on cell membranes[J]. EMBO J, 2020, 39(18): e105246. doi: 10.15252/embj.2020105246
|
| [14] |
Orinska Z, Hagemann PM, Halova I, et al. Tetraspanins in the regulation of mast cell function[J]. Med Microbiol Immunol, 2020, 209(4): 531-543. doi: 10.1007/s00430-020-00679-x
|
| [15] |
Vences-Catalán F, Duault C, Kuo CC, et al. CD81 as a tumor target[J]. Biochem Soc Trans, 2017, 45(2): 531-535. doi: 10.1042/BST20160478
|
| [16] |
Mazzocca A, Liotta F, Carloni V. Tetraspanin CD81-regulated cell motility plays a critical role in intrahepatic metastasis of hepatocellular carcinoma[J]. Gastroenterology, 2008, 135(1): 244-256. e1.
|
| [17] |
Yoo TH, Ryu BK, Lee MG, et al. CD81 is a candidate tumor suppressor gene in human gastric cancer[J]. Cell Oncol (Dordr), 2013, 36(2): 141-153. doi: 10.1007/s13402-012-0119-z
|
| [18] |
Lee MS, Kim JH, Lee JS, et al. Prognostic Significance of CREB-Binding Protein and CD81 Expression in Primary High Grade Non-Muscle Invasive Bladder Cancer: Identification of Novel Biomarkers for Bladder Cancer Using Antibody Microarray[J]. PLoS One, 2015, 10(4): e0125405. doi: 10.1371/journal.pone.0125405
|
| [19] |
Hong IK, Byun HJ, Lee J, et al. The tetraspanin CD81 protein increases melanoma cell motility by up-regulating metalloproteinase MT1-MMP expression through the pro-oncogenic Akt-dependent Sp1 activation signaling pathways[J]. J Biol Chem, 2014, 289(22): 15691-15704. doi: 10.1074/jbc.M113.534206
|
| [20] |
Mizoshiri N, Shirai T, Terauchi R, et al. The tetraspanin CD81 mediates the growth and metastases of human osteosarcoma[J]. Cell Oncol (Dordr), 2019, 42(6): 861-871.
|
| [21] |
Uretmen Kagiali ZC, Sanal E, Karayel Ö, et al. Systems-level Analysis Reveals Multiple Modulators of Epithelial-mesenchymal Transition and Identifies DNAJB4 and CD81 as Novel Metastasis Inducers in Breast Cancer[J]. Mol Cell Proteomics, 2019, 18(9): 1756-1771. doi: 10.1074/mcp.RA119.001446
|
| [22] |
Vences-Catalán F, Rajapaksa R, Srivastava MK, et al. Tetraspanin CD81 promotes tumor growth and metastasis by modulating the functions of T regulatory and myeloid-derived suppressor cells[J]. Cancer Res, 2015, 75(21): 4517-4526. doi: 10.1158/0008-5472.CAN-15-1021
|
| [23] |
Zheng W, Chen Q, Liu H, et al. CD81 Enhances Radioresistance of Glioblastoma by Promoting Nuclear Translocation of Rad51[J]. Cancers (Basel), 2021, 13(9): 1998. doi: 10.3390/cancers13091998
|
| [24] |
Signorelli D, Ghidotti P, Proto C, et al. Circulating CD81-expressing extracellular vesicles as biomarkers of response for immune-checkpoint inhibitors in advanced NSCLC[J]. Front Immunol, 2022, 13: 987639. doi: 10.3389/fimmu.2022.987639
|
| [25] |
Küppers R. CD81 as target for B cell lymphomas[J]. J Exp Med, 2019, 216(7): 1469-1470. doi: 10.1084/jem.20190733
|
| [26] |
Sermer D, Elavalakanar P, Abramson JS, et al. Targeting CD19 for diffuse large B cell lymphoma in the era of CARs: Other modes of transportation[J]. Blood Rev, 2023, 57: 101002. doi: 10.1016/j.blre.2022.101002
|
| [27] |
Susa KJ, Rawson S, Kruse AC, et al. Cryo-EM structure of the B cell co-receptor CD19 bound to the tetraspanin CD81[J]. Science, 2021, 371(6526): 300-305. doi: 10.1126/science.abd9836
|
| [28] |
Susa KJ, Seegar TC, Blacklow SC, et al. A dynamic interaction between CD19 and the tetraspanin CD81 controls B cell co-receptor trafficking[J]. Elife, 2020, 9: e52337. doi: 10.7554/eLife.52337
|
| [29] |
Velasquez MP, Gottschalk S. Targeting CD19: the good, the bad, and CD81[J]. Blood, 2017, 129(1): 9-10. doi: 10.1182/blood-2016-11-749143
|
| [30] |
Luo RF, Zhao S, Tibshirani R, et al. CD81 protein is expressed at high levels in normal germinal center B cells and in subtypes of human lymphomas[J]. Hum Pathol, 2010, 41(2): 271-280. doi: 10.1016/j.humpath.2009.07.022
|
| [31] |
Paiva B, Gutiérrez NC, Chen X, et al. Clinical significance of CD81 expression by clonal plasma cells in high-risk smoldering and symptomatic multiple myeloma patients[J]. Leukemia, 2012, 26(8): 1862-1869. doi: 10.1038/leu.2012.42
|
| [32] |
Paiva B, Puig N, Cedena MT, et al. Differentiation stage of myeloma plasma cells: biological and clinical significance[J]. Leukemia, 2017, 31(2): 382-392. doi: 10.1038/leu.2016.211
|
| [33] |
Boyer T, Guihard S, Roumier C, et al. Tetraspanin CD81 is an adverse prognostic marker in acute myeloid leukemia[J]. Oncotarget, 2016, 7(38): 62377-62385. doi: 10.18632/oncotarget.11481
|
| [34] |
Quagliano A, Gopalakrishnapillai A, Kolb EA, et al. CD81 knockout promotes chemosensitivity and disrupts in vivo homing and engraftment in acute lymphoblastic leukemia[J]. Blood Adv, 2020, 4(18): 4393-4405. doi: 10.1182/bloodadvances.2020001592
|
| [35] |
Braig F, Brandt A, Goebeler M, et al. Resistance to anti-CD19/CD3 BiTE in acute lymphoblastic leukemia may be mediated by disrupted CD19 membrane trafficking[J]. Blood, 2017, 129(1): 100-104. doi: 10.1182/blood-2016-05-718395
|
| [36] |
Ruella M, Korell F, Porazzi P, et al. Mechanisms of resistance to chimeric antigen receptor-T cells in haematological malignancies[J]. Nat Rev Drug Discov, 2023, 22(12): 976-995. doi: 10.1038/s41573-023-00807-1
|
| [37] |
Schultz LM, Czerwinski DK, Levy R, et al. CD81 costimulation skews CAR transduction toward naive T cells[J]. Proc Natl Acad Sci U S A, 2022, 119(5): e1910844119. doi: 10.1073/pnas.1910844119
|
| [38] |
Van Compernolle SE, Levy S, Todd SC. Anti-CD81 activates LFA-1 on T cells and promotes T cell-B cell collaboration[J]. Eur J Immunol, 2001, 31(3): 823-831. doi: 10.1002/1521-4141(200103)31:3<823::AID-IMMU823>3.0.CO;2-D
|
| [39] |
Vences-Catalán F, Kuo CC, Rajapaksa R, et al. CD81 is a novel immunotherapeutic target for B cell lymphoma[J]. J Exp Med, 2019, 216(7): 1497-1508. doi: 10.1084/jem.20190186
|
| [40] |
Vences-Catalán F, Rajapaksa R, Kuo CC, et al. Targeting the tetraspanin CD81 reduces cancer invasion and metastasis[J]. Proc Natl Acad Sci U S A, 2021, 118(24): e2018961118. doi: 10.1073/pnas.2018961118
|
| [41] |
Hasezaki T, Yoshima T, Mattsson M, et al. A monoclonal antibody recognizing a new epitope on CD81 inhibits T-cell migration without inducing cytokine production[J]. J Biochem, 2020, 167(4): 399-409. doi: 10.1093/jb/mvz103
|
| [42] |
Hasezaki T, Yoshima T, Mine Y. Anti-CD81 antibodies reduce migration of activated T lymphocytes and attenuate mouse experimental colitis[J]. Sci Rep, 2020, 10(1): 6969. doi: 10.1038/s41598-020-64012-5
|
| [43] |
Nelson B, Adams J, Kuglstatter A, et al. Structure-Guided Combinatorial Engineering Facilitates Affinity and Specificity Optimization of Anti-CD81 Antibodies[J]. J Mol Biol, 2018, 430(14): 2139-2152. doi: 10.1016/j.jmb.2018.05.018
|
| [44] |
Burkova EE, Dmitrenok PS, Bulgakov DV, et al. Exosomes from human placenta purified by affinity chromatography on sepharose bearing immobilized antibodies against CD81 tetraspanin contain many peptides and small proteins[J]. IUBMB Life, 2018, 70(11): 1144-1155. doi: 10.1002/iub.1928
|
| [45] |
Tan KL, Chia WC, How CW, et al. Benchtop Isolation and Characterisation of Small Extracellular Vesicles from Human Mesenchymal Stem Cells[J]. Mol Biotechnol, 2021, 63(9): 780-791. doi: 10.1007/s12033-021-00339-2
|
| [46] |
Fernandez L, Malrieu M, Bénistant C, et al. CD82 and Gangliosides Tune CD81 Membrane Behavior[J]. Int J Mol Sci, 2021, 22(16): 8459. doi: 10.3390/ijms22168459
|
| [47] |
Chuang ST, Papp H, Kuczmog A, et al. Methylene Blue Is aNonspecific Protein-Protein Interaction Inhibitor with Potential for Repurposing as an Antiviral for COVID-19[J]. Pharmaceuticals, 2022, 15(5): 621. doi: 10.3390/ph15050621
|
| [48] |
Anand K, Khan FI, Singh T, et al. Green Synthesis, Experimental and Theoretical Studies to Discover Novel Binders of Exosomal Tetraspanin CD81 Protein[J]. ACS Omega, 2020, 5(29): 17973-17982. doi: 10.1021/acsomega.0c01166
|
| [49] |
Moura AF, Lima KSB, Sousa TS, et al. In vitro antitumor effect of a lignan isolated from Combretum fruticosum, trachelogenin, in HCT-116 human colon cancer cells[J]. Toxicol In Vitro, 2018, 47: 129-136. doi: 10.1016/j.tiv.2017.11.014
|
| [50] |
Koech PK, Jócsák G, Boldizsár I, et al. Anti-glutamatergic Effects of Three Lignan Compounds: Arctigenin, Matairesinol and Trachelogenin-An ex vivo Study on Rat Brain Slices[J]. Planta Med, 2023, 89(9): 879-889. doi: 10.1055/a-2005-5497
|
| [51] |
Akella M, Malla R. Molecular modeling and in vitro study on pyrocatechol as potential pharmacophore of CD151 inhibitor[J]. J Mol Graph Model, 2020, 100: 107681. doi: 10.1016/j.jmgm.2020.107681
|
| [52] |
Kgk D, Kumari S, G S, et al. Marine natural compound cyclo(L-leucyl-L-prolyl) peptide inhibits migration of triple negative breast cancer cells by disrupting interaction of CD151 and EGFR signaling[J]. Chem Biol Interact, 2020, 315: 108872. doi: 10.1016/j.cbi.2019.108872
|
| [53] |
Mekky RY, El-Ekiaby N, El Sobky SA, et al. Epigallocatechin gallate (EGCG) and miR-548m reduce HCV entry through repression of CD81 receptor in HCV cell models[J]. Arch Virol, 2019, 164(6): 1587-1595. doi: 10.1007/s00705-019-04232-x
|
| [54] |
Mekky RY, El-Ekiaby NM, Hamza MT, et al. Mir-194 is a hepatocyte gate keeper hindering HCV entry through targeting CD81 receptor[J]. J Infect, 2015, 70(1): 78-87. doi: 10.1016/j.jinf.2014.08.013
|
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