Mechanism of Notch-1 in Tumor-associated Macrophages Affecting the In-vasion and Metastasis of Non-small Cell Lung Adenocarcinoma by Inhibi-ting the Overexpression of Cathepsin
Mechanism of Notch-1 in Tumor-associated Macrophages Affecting the In-vasion and Metastasis of Non-small Cell Lung Adenocarcinoma by Inhibi-ting the Overexpression of Cathepsin
Objective To explore the expression of Notch-1 in tumor-associated macrophages of non-small cell lung adenocarcinoma patients with and without liver metastasis,and to analyze its effect on cancer cell invasion and metastasis through in vitro cell culture and related mechanisms.Methods We collected specimens from 64 patients with non-small cell lung adenocarcinoma admitted from January 2021 to December 2022,and divided them into non-combined liver metastasis group(n=32)and combined liver metastasis group(n=32).Flow cytometry was performed to isolate CD68+tumor-associ-ated macrophages,and Western blot was used to detect the expression levels of Notch-1 in CD68+tumor-associated macropha-ges and related proteins in both groups.In vitro cultured human monocyte/macrophage THP-1 cells were infected with Notch-1 NC(negative control)and shRNA lentivirus vectors,respectively,and co-cultured with human non-small cell lung cancer A549.Western blot was used to detect the expression of THP-1 cell-related proteins,and Transwell assay and scratch assay were used to detect the migration and invasion ability of A549 cells in the co-culture system.Results Compared with the non-combined liver metastasis group,the expression level of Notch-1 in CD68+tumor-associated macrophages was significant-ly reduced in combined liver metastasis group,accompanied by a significant increase in the expression levels of arginase-1 and cathepsin S(P＜0.05).Compared with the Notch-1 NC group,the Notch-1 shRNA group had significantly reduced expres-sion level of Notch-1 in THP-1 cells and increased protein expression level of cathepsin S(P＜0.05).After co-culture with THP-1 cells infected with Notch-1 shRNA,the number of A549 cells expressing Notch-1 that inhibited invasion and migration significantly increased,and the distance of cell scratches significantly decreased(P＜0.05).Conclusion The Notch-1 pro-tein in tumor-associated macrophages has a role in inhibiting invasion and metastasis of non-small cell lung adenocarcinoma.
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