AIF1 + CSF1R + MSCs, induced by TNF‐α, act to generate an inflammatory microenvironment and promote hepatocarcinogenesis

Abstract

Background and Aims: Increasing evidence suggests that mesenchymal stem cells (MSCs) home to injured local tissues and the tumor microenvironment in the liver. Chronic inflammation is regarded as the major trait of primary liver cancer. However, the characteristics of endogenous MSCs in the inflammatory environment and their role in the occurrence of liver cancer remain obscure. Approach and Results: Using single-cell RNA sequencing, we identified a distinct inflammation-associated subset of MSCs, namely AIF1 + CSF1R + MSCs, which existed in the microenvironment before the occurrence of liver cancer. Furthermore, we found that this MSC subgroup is likely to be induced by TNF-α stimulation through the TNFR1/SIRT1 (sirtuin 1) pathway. In a rat primary liver cancer model, we showed that MSCs with high SIRT1 expression (Ad-Sirt1-MSCs) promoted macrophage recruitment and synergistically facilitated liver cancer occurrence by secreting C-C motif chemokine ligand (CCL) 5. Interestingly, depletion of macrophages or knockdown of CCL5 expression in Ad-Sirt1-MSCs attenuated the promotive effect of Ad-Sirt1-MSCs on liver inflammation and hepatocarcinogenesis (HCG). Finally, we demonstrated that SIRT1 up-regulated CCL5 expression through activation of the AKT/HIF1α signaling axis in MSCs. Conclusions: Together, our results show that MSCs, which are mobilized to the injured site, can be educated by macrophages. In turn, the educated

Allograft inflammatory factor 1 is a potential diagnostic, immunological, and prognostic biomarker in pan-cancer

“…Research by YANG et al also demonstrated that AIF-1 was an independent prognostic indicator that regulates the βcatenin signaling pathway in gastric cancer [40]. AIF-1 + CSF1R + MSCs, induced by TNF-α, generate an inflammatory microenvironment and promote hepatocarcinogenesis [41]. Furthermore, the PAK5-AIF signaling pathway may play an essential role in mammary tumorigenesis, providing a new therapeutic target for breast cancer treatment [42].…”

ALKBH5‐mediated m6A demethylation of TIRAP mRNA promotes radiation‐induced liver fibrosis and decreases radiosensitivity of hepatocellular carcinoma

“…Tumour volume was calculated using the formula: tumour volume (mm 3 ) = (smallest diameter 2 × largest diameter)/2. 38 The venous blood of mice was drawn from the eye orbit of mice, and then the mice were sacrificed at 3 weeks after the last irradiation. The levels of AST and ALT in serum were detected by an automatic biochemistry analyzer.…”

“…Tumour volume and liver/body weight ratio were evaluated at 3 weeks after the last irradiation. Tumour volume was calculated using the formula: tumour volume (mm 3 ) = (smallest diameter 2 × largest diameter)/2 38 . The venous blood of mice was drawn from the eye orbit of mice, and then the mice were sacrificed at 3 weeks after the last irradiation.…”

Bioadhesive Microcarriers Encapsulated with IL‐27 High Expressive MSC Extracellular Vesicles for Inflammatory Bowel Disease Treatment

“…[13][14][15][16][17] Preclinical and clinical studies have verified that the MSCs can mediate T cells activation and transform the function of dendritic cells and macrophages. [16,[18][19][20][21][22][23] However, MSC therapy has not achieved its desired clinical potential in IBD treatment because the therapeutic activity of naive seeding cells is limited. [24][25][26][27][28] In addition, existing intravenous injection strategy is generally systemic with several limitations such as poor targeting and fast metabolism.…”