Effect and mechanism of TGF-β on macrophage-derived cancer-associated fibroblasts in bladder can-cer tissue

Abstract

Objective To investigate the effect and mechanism of TGF-β on macrophage-derived cancer-associated fibroblasts (CAFs) in bladder cancer tissue. Methods The Kaplan-Meier method was used to investigate the relationship between the expression of α-SMA+CD68+CAF and overall survival (OS) in bladder cancer; immunofluorescence assay was used to observe the infiltration of α-SMA+CD68+CAF in bladder cancer tissue; Western blot was used to observe the inductive effect of TGF-β on α-SMA+CD68+CAF in vitro. A mouse model of bladder cancer was established, and immunofluorescence assay and immunohistochemistry were used to observe the inductive effect of TGF-β on α-SMA+CD68+CAF and its effect on the infiltration of CD8+T cells in mice with bladder cancer. Results The expression of α-SMA was positively correlated with that of CD68 in bladder can-cer tissue, and the patients with a high expression level of α-SMA+CD68+CAF tended to have a poorer prognosis (χ2=9.05,P<0.05). Immunofluorescence assay showed the presence of α-SMA+CD68+CAF in bladder cancer tissue, and Western blot showed that TGF-β could significantly promote the production of α-SMA+CD68+CAF. In vivo experiments in a mouse model of bladder cancer showed that TGF-β promoted the generation of α-SMA+CD68+CAF in bladder cancer tissue, thereby inhibiting the infiltration of CD8+T cells. Conclusion TGF-β can significantly promote the production of macrophage-derived CAF in bladder cancer tissue, thereby inhibiting the infiltration of CD8+T cells.

Keywords

• transforming growth factor beta|cancer-associated fibroblasts|urinary bladder neoplasms|tumor-asso-ciated macrophages|immune tolerance|cd8-positive t-lymphocytes|cell infiltration