Targeted Delivery of Diphtheria Toxin into VEGFR1/VEGFR2 Overexpressing Cells Induces Anti-angiogenesis Activity


Citar

Texto integral

Resumo

Background::Vascular Endothelial Growth Factor Receptors (VEGFR1 and VEGFR2) are tyrosine kinase receptors expressed on endothelial cells and tumor vessels and play an important role in angiogenesis. In this study, three repeats of VEGFR1 and VEGFR2 binding peptide (VGB3) were genetically fused to the truncated diphtheria toxin (TDT), and its in vitro activity was evaluated.

Methods::The recombinant construct (TDT-triVGB3) was expressed in bacteria cells and purified with nickel affinity chromatography. The binding capacity and affinity of TDT-triVGB3 were evaluated using the enzyme-linked immunosorbent assay. The inhibitory activity of TDT-triVGB3 on viability, migration, and tube formation of human endothelial cells was evaluated using MTT, migration, and tube formation assays.

Results::TDT-triVGB3 selectively detected VEGFR1 and VEGFR2 with high affinity in an enzyme- linked immunosorbent assay and significantly inhibited viability, migration, and tube formation of human endothelial cells.

Conclusion::The developed TDT-triVGB3 is potentially a novel agent for targeting VEGFR1/ VEGFR2 over-expressing cancer cells.

Sobre autores

Fatemeh Kazemi-Lomedasht

Venom and Biotherapeutics Molecules Laboratory, Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran

Autor responsável pela correspondência
Email: info@benthamscience.net

Farzad Taghizadeh-Hesary

ENT and Head and Neck Research Center and Department, The Five Senses Health Institute, School of Medicine, Iran University of Medical Sciences

Email: info@benthamscience.net

Zahra Faal

Venom and Biotherapeutics Molecules Laboratory, Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran

Email: info@benthamscience.net

Mahdi Behdani

Venom and Biotherapeutics Molecules Laboratory, Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran

Email: info@benthamscience.net

Bibliografia

  1. Lugano, R.; Ramachandran, M.; Dimberg, A. Tumor angiogenesis: Causes, consequences, challenges and opportunities. Cell. Mol. Life Sci., 2020, 77(9), 1745-1770. doi: 10.1007/s00018-019-03351-7 PMID: 31690961
  2. Mercurio, A. VEGF/neuropilin signaling in cancer stem cells. Int. J. Mol. Sci., 2019, 20(3), 490. doi: 10.3390/ijms20030490 PMID: 30678134
  3. Fearnley, G.W.; Smith, G.A.; Abdul-Zani, I.; Yuldasheva, N.; Mughal, N.A.; Homer-Vanniasinkam, S.; Kearney, M.T.; Zachary, I.C.; Tomlinson, D.C.; Harrison, M.A.; Wheatcroft, S.B.; Ponnambalam, S. VEGF-A isoforms program differential VEGFR2 signal transduction, trafficking and proteolysis. Biol. Open, 2016, 5(5), 571-583. doi: 10.1242/bio.017434 PMID: 27044325
  4. Otrock, Z.K.; Makarem, J.A.; Shamseddine, A.I. Vascular endothelial growth factor family of ligands and receptors: Review. Blood Cells Mol. Dis., 2007, 38(3), 258-268. doi: 10.1016/j.bcmd.2006.12.003 PMID: 17344076
  5. Karkkainen, M.J.; Petrova, T.V. Vascular endothelial growth factor receptors in the regulation of angiogenesis and lymphangiogenesis. Oncogene, 2000, 19(49), 5598-5605. doi: 10.1038/sj.onc.1203855 PMID: 11114740
  6. Lu, D.; Jimenez, X.; Zhang, H.; Wu, Y.; Bohlen, P.; Witte, L.; Zhu, Z. Complete inhibition of vascular endothelial growth factor (VEGF) activities with a bifunctional diabody directed against both VEGF kinase receptors, fms-like tyrosine kinase receptor and kinase insert domain-containing receptor. Cancer Res., 2001, 61(19), 7002-7008. PMID: 11585724
  7. Fischer, C.; Jonckx, B.; Mazzone, M.; Zacchigna, S.; Loges, S.; Pattarini, L.; Chorianopoulos, E.; Liesenborghs, L.; Koch, M.; De Mol, M.; Autiero, M.; Wyns, S.; Plaisance, S.; Moons, L.; van Rooijen, N.; Giacca, M.; Stassen, J.M.; Dewerchin, M.; Collen, D.; Carmeliet, P. Anti-PlGF inhibits growth of VEGF(R)-inhibitor-resistant tumors without affecting healthy vessels. Cell, 2007, 131(3), 463-475. doi: 10.1016/j.cell.2007.08.038 PMID: 17981115
  8. Wu, Y.; Zhong, Z.; Huber, J.; Bassi, R.; Finnerty, B.; Corcoran, E.; Li, H.; Navarro, E.; Balderes, P.; Jimenez, X.; Koo, H.; Mangalampalli, V.R.M.; Ludwig, D.L.; Tonra, J.R.; Hicklin, D.J. Anti-vascular endothelial growth factor receptor-1 antagonist antibody as a therapeutic agent for cancer. Clin. Cancer Res., 2006, 12(21), 6573-6584. doi: 10.1158/1078-0432.CCR-06-0831 PMID: 17085673
  9. Fan, F.; Schimming, A.; Jaeger, D.; Podar, K. Targeting the tumor microenvironment: Focus on angiogenesis. J. Oncol., 2012, 2012, 1-16. doi: 10.1155/2012/281261 PMID: 21876693
  10. Su, J-L.; Yen, C-J.; Chen, P-S.; Chuang, S-E.; Hong, C-C.; Kuo, I-H.; Chen, H-Y.; Hung, M-C.; Kuo, M-L. The role of the VEGF-C/VEGFR-3 axis in cancer progression. Br. J. Cancer, 2007, 96(4), 541-545. doi: 10.1038/sj.bjc.6603487 PMID: 17164762
  11. Sala, R.; Jefferies, W.A.; Walker, B.; Yang, J.; Tiong, J.; Law, S.K.A.; Carlevaro, M.F.; Di Marco, E.; Vacca, A.; Cancedda, R.; Cancedda, F.D.; Ribatti, D. The human melanoma associated protein melanotransferrin promotes endothelial cell migration and angiogenesis in vivo. Eur. J. Cell Biol., 2002, 81(11), 599-607. doi: 10.1078/0171-9335-00280 PMID: 12494997
  12. Ferrara, N. The role of VEGF in the regulation of physiological and pathological angiogenesis. EXS, 2005, 94(94), 209-231. doi: 10.1007/3-7643-7311-3_15 PMID: 15617481
  13. Brown, L.F.; Berse, B.; Jackman, R.W.; Tognazzi, K.; Guidi, A.J.; Dvorak, H.F.; Senger, D.R.; Connolly, J.L.; Schnitt, S.J. Expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in breast cancer. Hum. Pathol., 1995, 26(1), 86-91. doi: 10.1016/0046-8177(95)90119-1 PMID: 7821921
  14. Papetti, M.; Herman, I.M. Mechanisms of normal and tumor-derived angiogenesis. Am. J. Physiol. Cell Physiol., 2002, 282(5), C947-C970. doi: 10.1152/ajpcell.00389.2001 PMID: 11940508
  15. Brown, L.F.; Berse, B.; Jackman, R.W.; Tognazzi, K.; Manseau, E.J.; Dvorak, H.F.; Senger, D.R. Increased expression of vascular permeability factor (vascular endothelial growth factor) and its receptors in kidney and bladder carcinomas. Am. J. Pathol., 1993, 143(5), 1255-1262. PMID: 8238242
  16. Olson, T.A.; Mohanraj, D.; Carson, L.F.; Ramakrishnan, S. Vascular permeability factor gene expression in normal and neoplastic human ovaries. Cancer Res., 1994, 54(1), 276-280. PMID: 8261452
  17. Weidner, N.; Carroll, P.R.; Flax, J.; Blumenfeld, W.; Folkman, J. Tumor angiogenesis correlates with metastasis in invasive prostate carcinoma. Am. J. Pathol., 1993, 143(2), 401-409. PMID: 7688183
  18. Sadremomtaz, A.; Ali, A.M.; Jouyandeh, F.; Balalaie, S.; Navari, R.; Broussy, S.; Mansouri, K.; Groves, M.R.; Asghari, S.M. Molecular docking, synthesis and biological evaluation of Vascular Endothelial Growth Factor (VEGF) B based peptide as antiangiogenic agent targeting the second domain of the Vascular Endothelial Growth Factor Receptor 1 (VEGFR1D2) for anticancer application. Signal Transduct. Target. Ther., 2020, 5(1), 76. doi: 10.1038/s41392-020-0177-z PMID: 32499505
  19. Zanjanchi, P.; Asghari, S.M.; Mohabatkar, H.; Shourian, M.; Shafiee Ardestani, M. Conjugation of VEGFR1/R2-targeting peptide with gold nanoparticles to enhance antiangiogenic and antitumoral activity. J. Nanobiotechnology, 2022, 20(1), 7. doi: 10.1186/s12951-021-01198-4 PMID: 34980143
  20. Bennett, M.J.; Eisenberg, D. Refined structure of monomelic diphtheria toxin at 2.3 Å resolution. Protein Sci., 1994, 3(9), 1464-1475. doi: 10.1002/pro.5560030912 PMID: 7833808
  21. Kazemi-Lomedasht, F.; Behdani, M.; Pooshang Bagheri, K.; Habibi Anbouhi, M.; Abolhassani, M.; Khanahmad, H.; Shahbazzadeh, D.; Mirzahoseini, H. Expression and purification of functional human vascular endothelial growth factor-a121; the most important angiogenesis factor. Adv. Pharm. Bull., 2014, 4(4), 323-328. PMID: 25436186
  22. Zheng, W. Folding non-homologous proteins by coupling deep-learning contact maps with I-TASSER assembly simulations. Cell Rep. Meth., 2021, 1(3), 100014. doi: 10.1016/j.crmeth.2021.100014
  23. Zhang, C.; Freddolino, P.L.; Zhang, Y. COFACTOR: Improved protein function prediction by combining structure, sequence and protein–protein interaction information. Nucleic Acids Res., 2017, 45(W1), W291-W299. doi: 10.1093/nar/gkx366 PMID: 28472402
  24. Yang, J.; Zhang, Y. I-TASSER server: New development for protein structure and function predictions. Nucleic Acids Res., 2015, 43(W1), W174-W181. doi: 10.1093/nar/gkv342 PMID: 25883148
  25. Roshan, R.; Naderi, S.; Behdani, M.; Cohan, R.A.; Ghaderi, H.; Shokrgozar, M.A.; Golkar, M.; Kazemi-Lomedasht, F. Isolation and characterization of nanobodies against epithelial cell adhesion molecule as novel theranostic agents for cancer therapy. Mol. Immunol., 2021, 129, 70-77. doi: 10.1016/j.molimm.2020.10.021 PMID: 33183767
  26. Ahadi, M.; Ghasemian, H.; Behdani, M.; Kazemi-Lomedasht, F. Oligoclonal selection of nanobodies targeting vascular endothelial growth factor. J. Immunotoxicol., 2019, 16(1), 34-42. doi: 10.1080/1547691X.2018.1526234 PMID: 30409071
  27. Beatty, J.D.; Beatty, B.G.; Vlahos, W.G. Measurement of monoclonal antibody affinity by non-competitive enzyme immunoassay. J. Immunol. Methods, 1987, 100(1-2), 173-179. doi: 10.1016/0022-1759(87)90187-6 PMID: 2439600
  28. Shajari, S.; Farajollahi, M.M.; Behdani, M.; Tarighi, P. Production and conjugation of truncated recombinant diphtheria toxin to VEGFR-2 Specific nanobody and evaluation of its cytotoxic effect on PC-3 cell line. Mol. Biotechnol., 2022, 64(11), 1218-1226. doi: 10.1007/s12033-022-00485-1 PMID: 35478310
  29. Baharlou, R.; Tajik, N.; Behdani, M.; Shokrgozar, M.A.; Tavana, V.; Kazemi-Lomedasht, F.; Faraji, F.; Habibi-Anbouhi, M. An antibody fragment against human delta-like ligand-4 for inhibition of cell proliferation and neovascularization. Immunopharmacol. Immunotoxicol., 2018, 40(5), 368-374. doi: 10.1080/08923973.2018.1505907 PMID: 30183441
  30. Havaei, S.M.; Aucoin, M.G.; Jahanian-Najafabadi, A. Pseudomonas exotoxin-based immunotoxins: Over three decades of efforts on targeting cancer cells with the toxin. Front. Oncol., 2021, 11, 781800. doi: 10.3389/fonc.2021.781800 PMID: 34976821
  31. Behdani, M.; Zeinali, S.; Karimipour, M.; Khanahmad, H.; Schoonooghe, S.; Aslemarz, A.; Seyed, N.; Moazami-Godarzi, R.; Baniahmad, F.; Habibi-Anbouhi, M.; Hassanzadeh-Ghassabeh, G.; Muyldermans, S. Development of VEGFR2-specific nanobody pseudomonas exotoxin a conjugated to provide efficient inhibition of tumor cell growth. N. Biotechnol., 2013, 30(2), 205-209. doi: 10.1016/j.nbt.2012.09.002 PMID: 23031816

Arquivos suplementares

Arquivos suplementares
Ação
1. JATS XML
Baixar

Declaração de direitos autorais © Bentham Science Publishers, 2024