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Anti‑Axl monoclonal antibodies attenuate the migration of MDA‑MB‑231 breast cancer cells

  • Authors:
    • Hong Chang
    • Ran An
    • Xinying Li
    • Xiaoling Lang
    • Jiannan Feng
    • Ming Lv
  • View Affiliations / Copyright

    Affiliations: Institute of Medical Technology, Suzhou Vocational Health College, Suzhou, Jiangsu 215009, P.R. China, College of Basic Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei 050200, P.R. China, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, P.R. China, Beijing Key Laboratory of Therapeutic Gene Engineering Antibody, Beijing 100850, P.R. China
    Copyright: © Chang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 749
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    Published online on: August 27, 2021
       https://doi.org/10.3892/ol.2021.13010
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Abstract

The receptor tyrosine kinase, anexelekto (Axl) is involved in tumor cell growth, migration and invasion, and has been associated with chemotherapy resistance, which makes it an attractive target for cancer therapy. In total, six Axl‑targeted monoclonal antibodies (mAbs) and two antibody‑drug conjugates have been reported in the last 10 years, which have been shown to have bioactivity in inhibiting tumor cell proliferation and migration. The Axl external cell domain (Axl‑ECD), consisting of 426 amino acids, has always been used as an antigen in the screening process for all six of these Axl‑targeted mAbs. However, the Axl functional domain, which interacts with its natural ligand, growth arrest‑specific protein 6 (Gas6), is only a small part of the Axl‑ECD. Antibodies targeting the Axl functional domain may efficiently block Gas6‑Axl binding and attenuate its downstream signals and activities. To the best of our knowledge, no mAbs targeting the Axl functional domain have been reported. In the present study, a major Axl functional domain interacting with Gas6 was determined using bioinformatics and structural biology methods. In MDA‑MB‑231 breast cancer cell assays, anti‑Axl mAbs targeting this relatively specific Axl functional domain almost completely neutralized the stimulation of Gas6 in both Axl phosphorylation and cell migration assays, and showed similar activity to the positive control drug R428 (a small molecular tyrosine kinase inhibitor of Axl currently in phase II clinical trials) in the cell migration assay. Given the important role of Axl in tumor development and chemotherapy resistance, Axl‑targeted mAbs could be used to inhibit tumor cells directly, as well as reduce the development of chemotherapy resistance by blocking Axl activity. The application of Axl‑targeted mAbs combined with chemotherapy provides a promising treatment strategy for patients with tumors, particularly those with triple‑negative breast cancer, for whom no targeted therapy is currently available.
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Copy and paste a formatted citation
Spandidos Publications style
Chang H, An R, Li X, Lang X, Feng J and Lv M: Anti‑Axl monoclonal antibodies attenuate the migration of MDA‑MB‑231 breast cancer cells. Oncol Lett 22: 749, 2021.
APA
Chang, H., An, R., Li, X., Lang, X., Feng, J., & Lv, M. (2021). Anti‑Axl monoclonal antibodies attenuate the migration of MDA‑MB‑231 breast cancer cells. Oncology Letters, 22, 749. https://doi.org/10.3892/ol.2021.13010
MLA
Chang, H., An, R., Li, X., Lang, X., Feng, J., Lv, M."Anti‑Axl monoclonal antibodies attenuate the migration of MDA‑MB‑231 breast cancer cells". Oncology Letters 22.5 (2021): 749.
Chicago
Chang, H., An, R., Li, X., Lang, X., Feng, J., Lv, M."Anti‑Axl monoclonal antibodies attenuate the migration of MDA‑MB‑231 breast cancer cells". Oncology Letters 22, no. 5 (2021): 749. https://doi.org/10.3892/ol.2021.13010
Copy and paste a formatted citation
x
Spandidos Publications style
Chang H, An R, Li X, Lang X, Feng J and Lv M: Anti‑Axl monoclonal antibodies attenuate the migration of MDA‑MB‑231 breast cancer cells. Oncol Lett 22: 749, 2021.
APA
Chang, H., An, R., Li, X., Lang, X., Feng, J., & Lv, M. (2021). Anti‑Axl monoclonal antibodies attenuate the migration of MDA‑MB‑231 breast cancer cells. Oncology Letters, 22, 749. https://doi.org/10.3892/ol.2021.13010
MLA
Chang, H., An, R., Li, X., Lang, X., Feng, J., Lv, M."Anti‑Axl monoclonal antibodies attenuate the migration of MDA‑MB‑231 breast cancer cells". Oncology Letters 22.5 (2021): 749.
Chicago
Chang, H., An, R., Li, X., Lang, X., Feng, J., Lv, M."Anti‑Axl monoclonal antibodies attenuate the migration of MDA‑MB‑231 breast cancer cells". Oncology Letters 22, no. 5 (2021): 749. https://doi.org/10.3892/ol.2021.13010
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