Open Access

Construction and characterization of a truncated tissue factor‑coagulation‑based composite system for selective thrombosis in tumor blood vessels

  • Authors:
    • Peilan Xu
    • Mingyuan Zou
    • Shengyu Wang
    • Tingting Li
    • Cong Liu
    • Li Wang
    • Lanlan Wang
    • Fanghong Luo
    • Ting Wu
    • Jianghua Yan
  • View Affiliations

  • Published online on: August 12, 2019     https://doi.org/10.3892/ijo.2019.4855
  • Pages: 823-832
  • Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The selective induction of tumor vascular thrombosis using truncated tissue factor (tTF) delivered via a target ligand is a promising novel antitumor strategy. In the present study, an anti‑neuropilin‑1 (NRP‑1) monoclonal antibody (mAb)‑streptavidin (SA):tTF‑biotin (B) composite system was established. In this system, anti‑NRP‑1‑mAb located tTF to the tumor vascular endothelial cell surface and induced vascular embolization. Due to their high binding affinity, SA and B were used to enhance thrombogenic activity. mAb was conjugated with SA using a coupling method with water‑soluble 1‑ethyl‑3‑(3‑dimethylaminopropyl) carbodiimide and N‑hydroxysulfosuccinimide. Biotinylated tTF (tTF‑B) was prepared using a B‑labeling kit subsequent to the generation and purification of fusion protein tTF. Confocal microscopy and flow cytometry indicated that the anti‑NRP‑1‑mAb‑SA conjugate retained mAb targeting activity. The preservation of B‑conjugate binding capacity was confirmed using a competitive ELISA, and factor X‑activation analysis revealed that tTF‑B retained the procoagulant activity exhibited by tTF. Live imaging was performed to assess mAb‑SA distribution and tumor‑targeting capability, and this yielded promising results. The results of in vivo studies in mice with subcutaneous xenografts demonstrated that this composite system significantly induced tumor vascular thrombosis and inhibited tumor growth, whereas these histological changes were not observed in normal organs.

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October 2019
Volume 55 Issue 4

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Copy and paste a formatted citation
APA
Xu, P., Zou, M., Wang, S., Li, T., Liu, C., Wang, L. ... Yan, J. (2019). Construction and characterization of a truncated tissue factor‑coagulation‑based composite system for selective thrombosis in tumor blood vessels. International Journal of Oncology, 55, 823-832. https://doi.org/10.3892/ijo.2019.4855
MLA
Xu, P., Zou, M., Wang, S., Li, T., Liu, C., Wang, L., Wang, L., Luo, F., Wu, T., Yan, J."Construction and characterization of a truncated tissue factor‑coagulation‑based composite system for selective thrombosis in tumor blood vessels". International Journal of Oncology 55.4 (2019): 823-832.
Chicago
Xu, P., Zou, M., Wang, S., Li, T., Liu, C., Wang, L., Wang, L., Luo, F., Wu, T., Yan, J."Construction and characterization of a truncated tissue factor‑coagulation‑based composite system for selective thrombosis in tumor blood vessels". International Journal of Oncology 55, no. 4 (2019): 823-832. https://doi.org/10.3892/ijo.2019.4855