ISSN: 1837-9664Journal of Cancer
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J Cancer 2023; 14(1):114-128. doi:10.7150/jca.77888 This issue Cite
Research Paper
Anti-PAI-1 Monoclonal Antibody Inhibits the Metastasis and Growth of Esophageal Squamous Cell Carcinoma
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
Citation:
Zheng Y, Meng L, Qu L, Zhao C, Wang L, Liu C, Shou C. Anti-PAI-1 Monoclonal Antibody Inhibits the Metastasis and Growth of Esophageal Squamous Cell Carcinoma. J Cancer 2023; 14(1):114-128. doi:10.7150/jca.77888. https://www.jcancer.org/v14p0114.htm
Other stylesAbstract
Plasminogen activator inhibitor (PAI-1) is highly expressed in esophageal squamous cell carcinoma (ESCC) and strongly contributes to metastasis, making it a potential target for ESCC therapy. However, the antibodies and inhibitors targeting PAI-1 have not shown good therapeutic effect in the in vivo experiments yet. Here, we generated a panel of novel monoclonal antibodies (mAbs) against PAI-1. Analysis of PAI-1 expression in 90 tissue specimens and 128 serum specimens from ESCC patients with these mAbs confirmed that PAI-1 levels was significantly correlated with metastasis and poor survival. In addition, we found that high PAI-1 expression contributed to the enhanced motility and invasiveness of two ESCC cell lines. Next, mAb-1E2 and mAb-2E3, which have highest affinity with PAI-1, were shown to possess strong inhibitory effects on ESCC migration and invasion. Anti-tumor and anti-metastatic effects of mAb-2E3 were further demonstrated in the experimental animal models. Finally, LRP1 was identified as key factor mediating the pro-invasive function of PAI-1 and the anti-invasive capacity of mAb-2E3 in ESCC cells. The mAb-2E3 markedly decreased STAT1 phosphorylation levels and blocked the binding between PAI-1 and LRP1-ClusterII domain. Collectively, mAb-2E3 developed by our lab may be an effective antibody drug which can be used for anti-metastatic therapy in ESCC.
Keywords: Esophageal squamous cell carcinoma (ESCC), Plasminogen activator inhibitor (PAI-1), Monoclonal antibodies (mAb), Anti-tumor growth, Anti-metastasis
Citation styles
APA
Zheng, Y., Meng, L., Qu, L., Zhao, C., Wang, L., Liu, C., Shou, C. (2023). Anti-PAI-1 Monoclonal Antibody Inhibits the Metastasis and Growth of Esophageal Squamous Cell Carcinoma. Journal of Cancer, 14(1), 114-128. https://doi.org/10.7150/jca.77888.
ACS
Zheng, Y.; Meng, L.; Qu, L.; Zhao, C.; Wang, L.; Liu, C.; Shou, C. Anti-PAI-1 Monoclonal Antibody Inhibits the Metastasis and Growth of Esophageal Squamous Cell Carcinoma. J. Cancer 2023, 14 (1), 114-128. DOI: 10.7150/jca.77888.
NLM
Zheng Y, Meng L, Qu L, Zhao C, Wang L, Liu C, Shou C. Anti-PAI-1 Monoclonal Antibody Inhibits the Metastasis and Growth of Esophageal Squamous Cell Carcinoma. J Cancer 2023; 14(1):114-128. doi:10.7150/jca.77888. https://www.jcancer.org/v14p0114.htm
CSE
Zheng Y, Meng L, Qu L, Zhao C, Wang L, Liu C, Shou C. 2023. Anti-PAI-1 Monoclonal Antibody Inhibits the Metastasis and Growth of Esophageal Squamous Cell Carcinoma. J Cancer. 14(1):114-128.
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