IL-17A/IL-17RA promotes invasion and activates MMP-2 and MMP-9 expression via p38 MAPK signaling pathway in non-small cell lung cancer.

Abstract

The present study is to investigate the effect and mechanism of action of interleukin (IL)-17A and its receptor IL-17RA on non-small cell lung cancer (NSCLC). A total of 139 NSCLC patients were included in the study. NSCLC tissues and tumor-adjacent tissues were collected from the patients. Human NSCLC cell lines H157, H1975, and A549 were used for in vitro studies. MTT assay was performed to determine cell proliferation. Wound healing assay was used to determine cell motility. Transwell assay was carried out to detect migration and invasion. Quantitative real-time polymerase chain reaction was conducted to measure mRNA expression, while Western blotting was used for determine protein expression. Immunohistochemistry was employed to evaluate IL-17RA expression in 139 primary human NSCLC tissues. Levels of IL-17RA in NSCLC tissues were higher than tumor-adjacent normal tissues, and associated with clinical outcomes. Kaplan-Meier survival analysis indicated that NSCLC patients with positive IL-17RA expression had a poor survival. In addition, IL-17A/IL-17RA affected NSCLC cell migration and invasion in vitro. Treatment with IL-17A/IL-17RA increased the expression of MMP-2 and MMP-9 in NSCLC cells. Furthermore, phosphorylation of p38 was enhanced in IL-17RA-overexpressing NSCLC cells. P38 MAPK-specific inhibitor SB203580 suppressed the migration and invasion of NSCLC cells. MMP-2 and MMP-9 were downstream effectors of IL-17RA and p38 signaling pathways. The present study demonstrates that P38 MAPK activity is crucial for IL-17A/IL-17RA to promote NSCLC metastasis. In addition, IL-17A/IL-17RA signaling may be a novel and promising cancer therapeutic target for the treatment of NSCLC.

• Authors: Zhenhua Wu, Dan He, Shuyuan Zhao, Hongjiang Wang
• Journal: Molecular and cellular biochemistry (Mol Cell Biochem) Vol. 455 Issue 1-2 Pg. 195-206 (May 2019) ISSN: 1573-4919 [Electronic] Netherlands
• PMID: 30564960 (Publication Type: Clinical Trial, Journal Article)

Chemical References

• IL17A protein, human
• IL17RA protein, human
• Interleukin-17
• Neoplasm Proteins
• Receptors, Interleukin-17
• p38 Mitogen-Activated Protein Kinases
• MMP2 protein, human
• Matrix Metalloproteinase 2
• MMP9 protein, human
• Matrix Metalloproteinase 9

Topics

• Adult
• Aged
• Carcinoma, Non-Small-Cell Lung (metabolism, pathology)
• Female
• Humans
• Interleukin-17 (metabolism)
• Lung Neoplasms (metabolism, pathology)
• MAP Kinase Signaling System
• Male
• Matrix Metalloproteinase 2 (metabolism)
• Matrix Metalloproteinase 9 (metabolism)
• Middle Aged
• Neoplasm Invasiveness
• Neoplasm Proteins (metabolism)
• Receptors, Interleukin-17 (metabolism)
• p38 Mitogen-Activated Protein Kinases (metabolism)