Transferrin Receptor Serves as a Potential Target for Cancer Therapy
Transferrin receptor (TfR) is a glycoprotein that transfers iron from the extracellular matrix to the intracellular environment. Due to the rapid proliferation need, the demand for iron in cancer cells is much greater than in normal cells, possibly explaining the upregulated TfR expression in cancer cells. The overexpression of TfR and its extracellular accessibility, ability to internalize, and central role in cancer cell make this receptor a potential target for antibody-mediated therapy. The TfR can be targeted indirectly by antibodies conjugated to anti-cancer agents or directly through the use of antibodies that disrupt the function of the receptor and induce Fc-mediated effector functions. This article reviews the developments of antibody-based cancer therapy targeting TfR.
Cao JL, 2017, Research Progress of Transferrin Receptor in Tumor Targeted Therapy. Electron J Integra Tradit Chine Western Med Cardiovasc Dis, 5:16–17.
Han DM, Zhao YF, Li JL, et al, 2018, Progress of Transferrin Receptor in Tumor Research. J Fujian Normal Univ, 34:110–6.
Deng TH. The Relationship Between Transferrin Receptor and Tumor Diseases. Hainan Med, 22:137–40.
Daniels TR, Delgado T, Rodriguez JA, et al, 2006, The Transferrin Receptor Part I: Biology and Targeting with Cytotoxic Antibodies for the Treatment of Cancer. Clin Immunol, 121:144–58.
Daniels TR, Bernabeu E, Rodríguez JA, et al, 2012, Transferrin Receptors and the Targeted Delivery of Therapeutic Agents Against Cancer. Biochim Biophys Acta, 1820:291–317. DOI: 10.1016/j.bbagen.2011.07.016.
Wilner SE, Wengerter B, Maier K, et al, 2012, An RNA Alternative to Human Transferrin: A New Tool for Targeting Human Cells. Mol Ther Nucleic Acids. 1:e21. DOI: 10.1038/mtna.2012.14.
Yoon DJ, Liu CT, Quinlan DS, et al, 2011, Intracellular trafficking Considerations in the Development of Natural Ligand-drug Molecular Conjugates for Cancer. Ann Biomed Eng, 39:1235–51. DOI: 10.1007/s10439-011-0280-y.
De Vico G, Martano M, Maiolino P, et al, 2020, Expression of Transferrin Receptor-1 (TFR-1) in Canine Osteosarcomas. Vet Med Sci, 6:272–6. DOI: 10.1002/vms3.258.
Sugyo A, Tsuji AB, Sudo H, et al, 2015, Evaluation of Efficacy of Radioimmunotherapy with 90Y-labeled Fully Human Anti-transferrin Receptor Monoclonal Antibody in Pancreatic Cancer Mouse Models. PLoS One, 10:e0123761. DOI: 10.1371/journal.pone.0123761.
Kawamoto M, Horibe T, Kohno M, et al, 2011, A Novel Transferrin Receptor-targeted Hybrid Peptide Disintegrates Cancer Cell Membrane to Induce Rapid Killing of Cancer Cells. BMC Cancer, 11:359. DOI: 10.1186/1471-2407-11-359.
Moura IC, Centelles MN, Arcos-Fajardo M, et al, 2001, Identification of the Transferrin Receptor as a Novel Immunoglobulin (Ig)A1 Receptor and Its Enhanced Expression on Mesangial Cells in IgA Nephropathy. J Exp Med, 194:417–25. DOI: 10.1084/jem.194.4.417.
Xiao C, Fu X, Wang Y, et al, 2020, Transferrin Receptor Regulates Malignancies and the Stemness of Hepatocellular Carcinoma-derived Cancer Stem-like Cells by Affecting Iron Accumulation. PLoS One, 15:e0243812. DOI: 10.1371/journal.pone.0243812.
Greene CJ, Attwood K, Sharma NJ, et al, 2017, Transferrin Receptor 1 Upregulation in Primary Tumor and Downregulation in Benign Kidney is Associated with Progression and Mortality in Renal Cell Carcinoma Patients. Oncotarget, 8:107052–75. DOI: 10.18632/oncotarget.22323.
Ned RM, Swat W, Andrews NC, 2003, Transferrin Receptor 1 is Differentially Required in Lymphocyte Development. Blood, 102:3711–8. DOI: 10.1182/blood-2003-04-1086.
Bien-Ly N, Yu YJ, Bumbaca D, et al, 2014, Transferrin Receptor (TfR) Trafficking Determines Brain Uptake of TfR Antibody Affinity Variants. J Exp Med, 211:233–44. DOI: 10.1084/jem.20131660.
Chen T, Chen M, Chen J, 2013, Ionizing Radiation Potentiates Dihydroartemisinin-induced Apoptosis of A549 Cells Via a Caspase-8-dependent Pathway. PLoS One, 8:e59827. DOI: 10.1371/journal.pone.0059827.
Meng J, Yu H, Chen QR, 2010, Experience in Treating 1500 Cases of Malaria in Children with Artesunate. Ningxia Med J, 32:923-4.
Jeong S, Jing K, Kim N, et al, 2014, Docosahexaenoic Acid-induced Apoptosis is Mediated by Activation of Mitogen-activated Protein Kinases in Human Cancer Cells. BMC Cancer, 14:481. DOI: 10.1186/1471-2407-14-481.
Mi YJ, Geng GJ, Zou ZZ, et al, 2015, Dihydroartemisinin Inhibits Glucose Uptake and Cooperates with Glycolysis Inhibitor to Induce Apoptosis in Non-small Cell Lung Carcinoma Cells. PLoS One, 10:e0120426. DOI: 10.1371/journal.pone.0120426.
Zhao X, Zhong H, Wang R, et al, 2015, Dihydroartemisinin and Its Derivative Induce Apoptosis in Acute Myeloid Leukemia Through Noxa-mediated Pathway Requiring Iron and Endoperoxide Moiety. Oncotarget, 6:5582–96. DOI: 10.18632/oncotarget.3336.
Kong R, Jia G, Cheng ZX, et al. Dihydroartemisinin Enhances Apo2L/TRAIL-mediated Apoptosis in Pancreatic Cancer Cells Via ROS-mediated Up-regulation of Death Receptor 5. PLoS One, 7:e37222. DOI: 10.1371/journal.pone.0037222.
Disbrow GL, Baege AC, Kierpiec KA, 2005, Dihydroartemisinin is Cytotoxic to Papillomavirus Expressing Epithelial Cells in vitro and in vivo-Cancer Res, 65:10854–61. DOI: 10.1158/0008-5472.can-05-1216.
Zhang ZS, Wang J, Shen YB, et al, 2015, Dihydroartemisinin Increases Temozolomide Efficacy in Glioma Cells by Inducing Autophagy. Oncol Lett, 10:379–83.
Dong F, Zhou X, Li C, et al, 2014, Dihydroartemisinin Targets VEGFR2 Via the NF-kB Pathway in Endothelial Cells to Inhibit Angiogenesis. Cancer Biol Ther, 15:1479–88. DOI: 10.4161/15384047.2014.955728.
Rahman M, Kundu JK, Shin JW, et al, 2011, Docosahexaenoic Acid Inhibits UVB-induced Activation of NF-kB and Expression of COX-2 and NOX-4 in HR-1 Hairless Mouse Skin by Blocking MSK1 Signaling. PLoS One, 6:e28065. DOI: 10.1371/journal.pone.0028065.
Mercer AE, Maggs JL, Sun XM, et al, 2007, Evidence for the Involvement of Carbon-centered Radicals in the Induction of Apoptotic Cell Death by Artemisinin Compounds. J Biol Chem, 282:9372–82. DOI: 10.1074/jbc.m610375200.
Ferreira JF, Luthria DL, Sasaki T, et al, 2010, Flavonoids from Artemisia annua L. As Antioxidants and Their Potential Synergism with Artemisinin Against Malaria and Cancer. Molecules, 15:3135–70. DOI: 10.3390/molecules15053135.
Zhang CZ, Zhang H, Yun J, et al, 2012, Dihydroartemisinin Exhibits Antitumor Activity Toward Hepatocellular Carcinoma in vitro and in vivo. Biochem Pharmacol, 83:1278–89. DOI: 10.1016/j.bcp.2012.02.002.
Mu D, Zhang W, Chu D, et al, 2008, The Role of Calcium, P38 MAPK in Dihydroartemisinin-induced Apoptosis of Lung Cancer PC-14 Cells. Cancer Chemother Pharmacol, 61:639–45. DOI: 10.1007/s00280-007-0517-5.
He Q, Shi J, Shen XL, et al, 2010, Dihydroartemisinin Upregulates Death Receptor 5 Expression and Cooperates with TRAIL to Induce Apoptosis in Human Prostate Cancer Cells. Cancer Biol Ther, 9:819–24. DOI: 10.4161/cbt.9.10.11552.
Kvansakul M, Hinds MG, 2013, Structural Biology of the Bcl-2 Family and its Mimicry by Viral Proteins. Cell Death Dis, 4:e909. DOI: 10.1038/cddis.2013.436.
Luo M, Lewik G, Ratcliffe JC, et al, 2019, Systematic Evaluation of Transferrin-modified Porous Silicon Nanoparticles for Targeted Delivery of Doxorubicin to Glioblastoma. ACS Appl Mater Interfaces, 11:33637–49. DOI: 10.1021/acsami.9b10787.
Shen Y, Li X, Dong D, et al, 2018, Transferrin Receptor 1 in Cancer: A New Sight for Cancer Therapy. Am J Cancer Res, 8:916–31.
Li S, Zhao H, Mao X, et al, 2019, Transferrin Receptor Targeted Cellular Delivery of Doxorubicin Via a Reduction-responsive Peptide-drug Conjugate. Pharm Res, 36:168. DOI: 10.1007/s11095-019-2688-2.
Kawabata H, 2019, Transferrin and Transferrin Receptors Update. Free Radic Biol Med, 133:46–54. DOI: 10.1016/j.freeradbiomed.2018.06.037.
Feng H, Schorpp K, Jin J, et al, 2020, Transferrin Receptor is a Specific Ferroptosis Marker. Cell Rep, 30:3411–23.e7.
Shao M, Liu Y, 2014, Research Progress in Targeted Therapy of Tumors and Brain Diseases Based on Transferrin Receptor (TfR1) [J]. Med Inform, 16:657–9.