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Journal of Experimental & Clinical Cancer Research

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Open Access 01-12-2024 | NSCLC | Research

Gli1-mediated tumor cell-derived bFGF promotes tumor angiogenesis and pericyte coverage in non-small cell lung cancer

Authors: Xueping Lei, Zhan Li, Manting Huang, Lijuan Huang, Yong Huang, Sha Lv, Weisong Zhang, Zhuowen Chen, Yuanyu Ke, Songpei Li, Jingfei Chen, Xiangyu Yang, Qiudi Deng, Junshan Liu, Xiyong Yu

Published in: Journal of Experimental & Clinical Cancer Research | Issue 1/2024

Abstract

Background

Tumor angiogenesis inhibitors have been applied for non-small cell lung cancer (NSCLC) therapy. However, the drug resistance hinders their further development. Intercellular crosstalk between lung cancer cells and vascular cells was crucial for anti-angiogenenic resistance (AAD). However, the understanding of this crosstalk is still rudimentary. Our previous study showed that Glioma-associated oncogene 1 (Gli1) is a driver of NSCLC metastasis, but its role in lung cancer cell-vascular cell crosstalk remains unclear.

Methods

Conditioned medium (CM) from Gli1-overexpressing or Gli1-knockdown NSCLC cells was used to educate endothelia cells and pericytes, and the effects of these media on angiogenesis and the maturation of new blood vessels were evaluated via wound healing assays, Transwell migration and invasion assays, tube formation assays and 3D coculture assays. The xenograft model was conducted to establish the effect of Gli1 on tumor angiogenesis and growth. Angiogenic antibody microarray analysis, ELISA, luciferase reporte, chromatin immunoprecipitation (ChIP), bFGF protein stability and ubiquitination assay were performed to explore how Gli1 regulate bFGF expression.

Results

Gli1 overexpression in NSCLC cells enhanced the endothelial cell and pericyte motility required for angiogenesis required for angiogenesis. However, Gli1 knockout in NSCLC cells had opposite effect on this process. bFGF was critical for the enhancement effect on tumor angiogenesis. bFGF treatment reversed the Gli1 knockdown-mediated inhibition of angiogenesis. Mechanistically, Gli1 increased the bFGF protein level by promoting bFGF transcriptional activity and protein stability. Importantly, suppressing Gli1 with GANT-61 obviously inhibited angiogenesis.

Conclusion

The Gli1-bFGF axis is crucial for the crosstalk between lung cancer cells and vascular cells. Targeting Gli1 is a potential therapeutic approach for NSCLC angiogenesis.

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Title: Gli1-mediated tumor cell-derived bFGF promotes tumor angiogenesis and pericyte coverage in non-small cell lung cancer
Authors: Xueping Lei
Zhan Li
Manting Huang
Lijuan Huang
Yong Huang
Sha Lv
Weisong Zhang
Zhuowen Chen
Yuanyu Ke
Songpei Li
Jingfei Chen
Xiangyu Yang
Qiudi Deng
Junshan Liu
Xiyong Yu
Publication date: 01-12-2024
Publisher: BioMed Central
Keywords: NSCLC
NSCLC
Published in: Journal of Experimental & Clinical Cancer Research / Issue 1/2024
Electronic ISSN: 1756-9966
DOI: https://doi.org/10.1186/s13046-024-03003-0

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