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

Yutian Zheng, Lin Meng, Like Qu, Chuanke Zhao, Lixin Wang, Caiyun Liu, Chengchao Shou

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
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Abstract

Graphic abstract

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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