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Archive > Volume 29 Issue 9 > 2022,29(9):797-805. DOI:10.3872/j.issn.1007-385X.2022.09.003 Prev Next
Basic Research
The mechanism and relative significance of carboxypeptidase A4 promoting the proliferation, migration, invasion and EMT of non-small cell lung cancer cells
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Abstract:
Objective: To explore the mechanism and clinical significance of carboxypeptidase A4 (CPA4) promoting the proliferation,migration, invasion and epithelial-mesenchymal transformation (EMT) progression of non-small cell lung cancer (NSCLC) cells.Methods: IHC and WB were employed to detect the expression of CPA4 in NSCLC tissues and adjacent tissues of 105 patients with advanced or metastatic NSCLC in Jinan Central Hospital from February 2012 to December 2015 and the expression of CPA4 in NSCLC cells. Chi-square test was used to analyze the association between CPA4 expression and the clinicopathological characteristics of the patients. The relationship between CPA4 expression and the overall survival (OS) of the patients was analyzed by Kaplan-Meier method. H1299 and A549 NSCLC cells with stable overexpression and downexpression of CPA4 were constructed by cell transfection.Changes in the cell proliferation, invasion and migration after overexpression and knockdown of CPA4 were detected by CCK-8 assay,cell colony formation assay, scratch healing assay and Transwell assay. Xenograft tumor models and tail vein‐lung metastasis tumor models of nude mice were established to detect the role of CPA4 in tumor tumorigenesis and metastasis in vivo. Changes in the markers of EMT in the tissues of xenografts were detected by WB and IHC. Results: Compared with paracancer tissues and normal lung epithelial cells, CPA4 was highly expressed in cancer tissues and cancer cells (all P?0.05). The OS of NSCLC patients with high CPA4 expression was significantly shorter than that of patients with low CPA4 expression (P?0.05). High expression of CPA4 was more common in poor differentiation, N2-3 lymph node involvement and TNM stage Ⅳ (P?0.05 or P?0.01). Overexpression of CPA4 promoted H1299 cells, while knockdown of CPA4 inhibited the proliferation, migration and invasion of A549 cells. Overexpression of CPA4 promoted the growth of H1299 cell xenograft tumors and lung metastatic tumors in nude mice. Overexpression of CPA4 promoted the changes of EMT process-related molecules in H1299 cells. Conclusion: CPA4 is highly expressed in NSCLC tissues and cells. Overexpression of CPA4 can induce EMT, promote the proliferation，migration and invasion of NSCLC cells and is related to tumor progression and prognosis. CPA4 is a potential biomarker for predicting relapse and prognosis of NSCLC and can be used for targeted therapy.
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