Anti-PRL-3 Monoclonal Antibody inhibits the Growth and Metastasis of colorectal adenocarcinoma

Shuning Sun; Lin Meng; Xiaofang Xing; Ningning Li; Qian Song; Dongbo Qiao; Like Qu; Caiyun Liu; Guo An; Zhongwu Li; Chenchao Shou; Shenyi Lian

doi:10.7150/jca.81702

Anti-PRL-3 Monoclonal Antibody inhibits the Growth and Metastasis of colorectal adenocarcinoma

J Cancer. 2023 Aug 21;14(13):2585-2595. doi: 10.7150/jca.81702. eCollection 2023.

Authors

Shuning Sun¹, Lin Meng¹, Xiaofang Xing², Ningning Li³, Qian Song⁴, Dongbo Qiao³, Like Qu¹, Caiyun Liu¹, Guo An⁵, Zhongwu Li³, Chenchao Shou¹, Shenyi Lian³

Affiliations

¹ Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Biochemistry and Molecular Biology, Peking University Cancer Hospital & Institute, Beijing, China.
² Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Gastrointestinal Translational Research, Peking University Cancer Hospital & Institute, Beijing, China.
³ Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Pathology, Peking University Cancer Hospital & Institute, Beijing, China.
⁴ Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, Zhejiang, China.
⁵ Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Laboratory Animal, Peking University Cancer Hospital & Institute, Beijing, China.

Abstract

Background: Colon cancer is the one of leading causes of cancer-related death. Chemotherapy, radiotherapy and immunotherapy will be the mainstream in inoperable advanced cancer in clinics. Precision treatment is still lack in colon cancer. Materials and Methods: We developed a series of mAbs targeting PRL-3 through different types of immunogens. The binding domains of mAbs were identified through the ELISA and Western blotting experiments. The antitumor activity of mAbs was verified by cell proliferation, migration and invasion experiments. Xenograft subcutaneous and metastatic models and patient derived Xenograft (PDX) model were established. Results: mAb 12G12 targeting 77-120AA exhibited inhibition in migration and invasion experiments. 12G12 inhibited the migration of multiple types of cancer cells, including colon cancer, gastric cancer, esophagus cancer, liver cancer, lung cancer and pancreatic cancer cells. 12G12 decreased the tumor growth and metastasis in Xenograft subcutaneous and metastatic tumor model, respectively. The antitumor activity of mAb 12G12 was also confirmed in PDX model of gastric cancer. PRL-3 interacted with Golgi protein TMED10. Knockdown of TMED10 expression attenuated the cell migration triggered by purified GST-PRL-3 protein. Conclusion: Our results confirmed the antitumor activity of mAb 12G12 in colorectal adenocarcinoma and provided a new potential targeted therapy of colon cancer.

Keywords: PRL-3; colon cancer; metastasis; monoclonal antibody.