PMID- 37160564 OWN - NLM STAT- MEDLINE DCOM- 20240118 LR - 20240202 IS - 1559-0291 (Electronic) IS - 0273-2289 (Linking) VI - 196 IP - 1 DP - 2024 Jan TI - Expression and Purification of FGFR1-Fc Fusion Protein and Its Effects on Human Lung Squamous Carcinoma. PG - 573-587 LID - 10.1007/s12010-023-04542-6 [doi] AB - 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. CI - (c) 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Zheng, Lulu AU - Zheng L AD - School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China. AD - Department of Pharmacy, Tongde Hospital of Zhejiang Province, Zhejiang, 310000, Hangzhou, China. FAU - Liu, Huan AU - Liu H AD - School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China. FAU - Chen, Lingfeng AU - Chen L AD - School of Pharmaceutical Sciences, Hangzhou Medical College, Zhejiang, 310012, Hangzhou, China. FAU - You, Xinyi AU - You X AD - School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China. FAU - Lv, Fangyi AU - Lv F AD - School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China. FAU - Fan, Haibing AU - Fan H AD - School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China. FAU - Hui, Qi AU - Hui Q AD - School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China. huiqi1976@163.com. FAU - Liu, Baohua AU - Liu B AD - School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China. bhbh369@wmu.edu.cn. AD - Department of Neurological Rehabilitation, The Second Asffiliated Hospital of Wenzhou Medical University, Wenzhou, 325035, China. bhbh369@wmu.edu.cn. FAU - Wang, Xiaojie AU - Wang X AD - School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, Zhejiang, 325035, China. susanwang1214@wmu.edu.cn. LA - eng PT - Journal Article DEP - 20230509 PL - United States TA - Appl Biochem Biotechnol JT - Applied biochemistry and biotechnology JID - 8208561 RN - CTG26PRE5S (FP-1039) RN - 103107-01-3 (Fibroblast Growth Factor 2) RN - EC 2.7.10.1 (Receptor, Fibroblast Growth Factor, Type 1) RN - EC 2.7.10.1 (FGFR1 protein, human) RN - 0 (Immunoglobulin G) RN - 0 (Recombinant Fusion Proteins) SB - IM MH - Humans MH - Fibroblast Growth Factor 2 MH - Receptor, Fibroblast Growth Factor, Type 1/genetics/metabolism MH - *Carcinoma, Non-Small-Cell Lung MH - Cell Proliferation MH - *Carcinoma, Squamous Cell/genetics MH - *Lung Neoplasms/drug therapy MH - Lung/metabolism MH - Cell Line, Tumor MH - *Immunoglobulin G MH - *Recombinant Fusion Proteins OTO - NOTNLM OT - FGF2 OT - FGFR1 OT - FGFR1-Fc fusion protein OT - Squamous cell carcinoma EDAT- 2023/05/10 00:41 MHDA- 2024/01/18 06:42 CRDT- 2023/05/09 22:50 PHST- 2023/04/11 00:00 [accepted] PHST- 2024/01/18 06:42 [medline] PHST- 2023/05/10 00:41 [pubmed] PHST- 2023/05/09 22:50 [entrez] AID - 10.1007/s12010-023-04542-6 [pii] AID - 10.1007/s12010-023-04542-6 [doi] PST - ppublish SO - Appl Biochem Biotechnol. 2024 Jan;196(1):573-587. doi: 10.1007/s12010-023-04542-6. Epub 2023 May 9.