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Expression and Purification of FGFR1-Fc Fusion Protein and Its Effects on Human Lung Squamous Carcinoma

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Abstract

Molecular-targeted therapies for lung squamous cell carcinoma (LSCC) are limited mainly because targetable oncogenic aberrations are absent in LSCC. Recent genomic analyses have revealed that the fibroblast growth factor (FGF) signaling pathway plays a fundamental role in LSCC progression via cancer cell proliferation and angiogenesis. In the present study, we designed, expressed, and purified a fibroblast growth factor receptor fragment (FGFR1-Fc) fusion protein using NS/0 cells. In FGF2-FGFR1 overexpressed NCI-H1703 cells, the FGFR1-Fc fusion protein effectively inhibited proliferation and invasion and arrested the cell cycle at the G0-G1 phase. In NCI-H1703 cells treated with the FGFR1-Fc fusion protein, the phosphorylation levels of FGFR1, FRS2, ERK, and AKT were significantly reduced. Using an siRNA assay, we demonstrated that FGF2-FGFR1 is the major anti-tumor target of FGFR1-Fc fusion the FGFR1-Fc fusion protein, which also significantly inhibited proliferation and invasion by NCI-H1703 cells via the FGF2-FGFR1 signaling pathway. In addition, the FGFR1-Fc fusion protein significantly inhibited angiogenesis in an embryonic chorioallantoic membrane model. The FGFR1-Fc fusion protein may be an effective therapeutic candidate for LSCC.

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Funding

This work was supported by the Natural Science Funding of Zhejiang Province (LYY19H310006 to L.Z., Y21H150027) and the Science and technology plan project of Wenzhou City (Y20150105).

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Authors and Affiliations

  1. School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China

    Lulu Zheng, Huan Liu, Xinyi You, Fangyi Lv, Haibing Fan, Qi Hui, Baohua Liu & Xiaojie Wang

  2. Department of Pharmacy, Tongde Hospital of Zhejiang Province, Zhejiang, 310000, Hangzhou, China

    Lulu Zheng

  3. School of Pharmaceutical Sciences, Hangzhou Medical College, Zhejiang, 310012, Hangzhou, China

    Lingfeng Chen

  4. Department of Neurological Rehabilitation, The Second Asffiliated Hospital of Wenzhou Medical University, Wenzhou, 325035, China

    Baohua Liu

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  1. Lulu Zheng
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  9. Xiaojie Wang
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Contributions

(I) Conception and design: L. Zheng; (II) Administrative support: Q. Hui, B. Liu, X. Wang; (III) Provision of study materials or patients: L. Chen; (IV) Collection and assembly of data: H. Liu, X You; (V) Data analysis and interpretation: F Lv, H. Fan; (VI) Organize and reply to major revision: H. Wang; (VII) Manuscript writing: All authors; (VIII) Final approval of manuscript: All authors.

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Correspondence to Qi Hui, Baohua Liu or Xiaojie Wang.

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Zheng, L., Liu, H., Chen, L. et al. Expression and Purification of FGFR1-Fc Fusion Protein and Its Effects on Human Lung Squamous Carcinoma. Appl Biochem Biotechnol 196, 573–587 (2024). https://doi.org/10.1007/s12010-023-04542-6

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