FSCN1 induced PTPRF-dependent tumor microenvironment inflammatory reprogramming promotes lung adenocarcinoma progression via regulating macrophagic glycolysis.

Abstract

PURPOSE:

Macrophages (MΦs) play a dual role in the promotion and suppression of lung adenocarcinoma (LUAD), the function of which is influenced by the metabolic status. The role of protein tyrosine phosphatase receptor type F (PTPRF) in cancer has not been elucidated, and its role in MΦs remains to be seen.

METHODS:

The Seahorse XFe 96 Cell Flow Analyzer detected glucose metabolism in tumor cells and macrophages. The expressions of FSCN1, M-CSF, IL4, PTPRF and IGF1 in macrophages were detected by Western blotting and qRT-PCR. Binding of FSCN1 and IGF1R was detected by co-immunoprecipitation. The tumor status in animals was observed using the IVIS Lumina III imaging system.

RESULTS:

We found that Fascin Actin-Bundling Protein 1 (FSCN1) activates the PI3K-AKT and JAK-STAT signaling pathways in LUAD cells via binding to IGF-1R, thereby promoting the secretion of cytokines such as IL4 and M-CSF. IL4 and M-CSF promote the expression of PTPRF in MΦs, leading to M2 polarization of MΦs by increasing glucose intake and lactate production. In return, M2-type MΦs act on LUAD cells by secreting cytokines such as IGF-1, CCL2, and IL10, which ultimately promote tumor progression. In vivo experiments proved that the knockdown of FSCN1 in A549 cells and PTPRF in MΦs greatly reduced LUAD proliferative and metastatic capacity, which was consistent with the in vitro findings.

CONCLUSIONS:

This study investigated the reprogramming effects of FSCN1 and PTPRF on inflammatory cytokines in the LUAD microenvironment, revealing potential mechanisms by which FSCN1 and PTPRF promote tumor progression and providing a new experimental basis for LUAD treatment.

• Authors: Yiwei Huang, Guangyao Shan, Yanjun Yi, Jiaqi Liang, Zhengyang Hu, Guoshu Bi, Zhencong Chen, Junjie Xi, Di Ge, Qun Wang, Lijie Tan, Wei Jiang, Cheng Zhan
• Journal: Cellular oncology (Dordrecht) (Cell Oncol (Dordr)) Vol. 45 Issue 6 Pg. 1383-1399 (Dec 2022) ISSN: 2211-3436 [Electronic] Netherlands
• PMID: 36223033 (Publication Type: Journal Article)
• Copyright: © 2022. Springer Nature Switzerland AG.

Chemical References

• Macrophage Colony-Stimulating Factor
• Phosphoric Monoester Hydrolases
• Interleukin-4
• Phosphatidylinositol 3-Kinases
• Cytokines

Topics

• Animals
• Tumor Microenvironment
• Macrophage Colony-Stimulating Factor (metabolism)
• Phosphoric Monoester Hydrolases (metabolism)
• Interleukin-4 (metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Cell Proliferation
• Adenocarcinoma of Lung (metabolism)
• Macrophages (metabolism)
• Cytokines (metabolism)
• Glycolysis
• Lung Neoplasms (pathology)
• Gene Expression Regulation, Neoplastic