A20 affects macrophage polarization through the NLRP3 inflammasome signaling pathway and promotes breast cancer progression

Abstract

Breast cancer is the most common malignant tumor in females, and the majority of patients succumb to metastasis. The present study aimed to investigate the association between tumor necrosis factor alpha-induced protein 3 (A20), NOD-, LRR-and pyrin domain-containing protein 3 (NLRP3) and tumor-associated macrophage polarization, and their effects on the proliferation and metastasis of breast cancer cells. The expression of A20 in breast cancer cells was analyzed by reverse transcription-quantitative PCR (RT-qPCR) and western blotting. RT-qPCR and western blotting were also used to confirm the transfection efficiency. The viability, clone formation, migration, invasion and angiogenesis of transfected breast cancer cells were detected by Cell Counting Kit-8, colony formation, wound healing, Transwell and tube formation assays, respectively. Activated macrophages, namely M1 and M2 type macrophages, were observed by double staining immunofluorescence. The levels of M1 and M2 macrophage markers were analyzed by qPCR. The expression of angiogenesis-related proteins and NLRP3 inflammasome activation-associated proteins was detected by western blotting. The results revealed that A20 was highly expressed in breast cancer cells. Interference with A20 inhibited the proliferation, invasion, migration and angiogenesis of breast cancer cells, and inhibited the M2-like polarization of macrophages. Interference with A20 promoted the activation of the NLRP3 inflammasome. The NLRP3 inhibitor MCC950 alleviated the effect of interference with A20 to promote macrophage proliferation and recruitment, as well as M2-like polarization. In conclusion, interference with A20 inhibited macrophage proliferation and M2-like polarization through the NLRP3 inflammasome signaling pathway to inhibit breast cancer progression.

Macrophage plasticity: signaling pathways, tissue repair, and regeneration

“…SOCS proteins inhibit the JAK–STAT signaling pathway, which produces proinflammatory cytokines, while A20 negatively regulates the NF‐κB signaling pathway, a central regulator of inflammation. 345 , 346 , 347 Additionally, M2 macrophages produce anti‐inflammatory lipid mediators, such as lipoxins, resolvins, and protectins, which can actively suppress proinflammatory signaling pathways and promote the clearance of apoptotic cells and debris. 348 …”

Measuring and modeling macrophage proliferation in a lab-on-CMOS capacitance sensing microsystem

“…For instance, atherosclerotic plaque progression and rupture can be fueled by macrophage-mediated inflammation (Tang et al, 2015). In another example, tumorassociated macrophages (TAMs) can produce chemokines that in turn promote tumor metastasis, immune escape, and lung metastasis in breast cancer (Zheng et al, 2023). In yet another example, the inflammatory responses involving infiltration and activation of liver macrophages can play a vital role in acute liver failure (Cai et al, 2023).…”