IL-35 promotes EMT through STAT3 activation and induces MET by promoting M2 macrophage polarization in HCC

Area of Science:

• Oncology
• Immunology
• Cell Biology

Background:

• The tumor microenvironment significantly influences cancer progression, including tumor growth and metastasis.
• Macrophage polarization states are critical components of the tumor microenvironment, impacting cancer cell behavior.

Purpose of the Study:

• To investigate the role of macrophage polarization in regulating epithelial-mesenchymal transition (EMT) and mesenchymal-epithelial transition (MET) in hepatocellular carcinoma (HCC).
• To determine the effect of Interleukin-35 (IL-35), secreted by M1 macrophages, on EMT and MET in HCC cells.

Main Methods:

• Analysis of IL-35 levels secreted by M1 and M2 macrophages.
• Assessment of EMT and MET induction in HCC cells treated with IL-35.
• Investigation of STAT3 activation pathways in response to IL-35.
• Evaluation of IL-35's indirect effects on MET through M2 macrophage polarization.

Main Results:

• M1 macrophages secreted significantly higher levels of IL-35 compared to M2 macrophages.
• IL-35 facilitated EMT in HCC cells, primarily through the activation of STAT3.
• IL-35 did not directly induce MET but indirectly promoted MET in HCC cells via M2 macrophage polarization.

Conclusions:

• Macrophage polarization and IL-35 secretion play crucial roles in regulating epithelial plasticity in HCC.
• IL-35 acts as a key mediator in the interplay between macrophages and HCC cells, influencing EMT and MET.
• Modulating IL-35 levels or macrophage polarization presents potential therapeutic strategies for targeting HCC metastasis.