Circulating AIM prevents hepatocellular carcinoma through complement activation.

Area of Science:

• Hepatology
• Immunology
• Oncology

Background:

• Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality worldwide.
• The role of circulating proteins in HCC pathogenesis and treatment remains an active area of research.

Purpose of the Study:

• To investigate the anti-HCC effects of the circulating protein AIM.
• To elucidate the mechanism by which AIM impacts HCC development and progression.

Main Methods:

• Utilized AIM(-/-) and wild-type mice models.
• Administered AIM and diethylnitrosamine for HCC induction.
• Analyzed liver inflammation, fibrosis, and tumor development.
• Investigated AIM's interaction with hepatocytes and HCC cells.

Main Results:

• AIM(-/-) mice exhibited high susceptibility to steatosis-associated HCC, unlike AIM(+/+) mice.
• AIM administration prevented tumor development in AIM(-/-) mice.
• AIM accumulates on HCC cell surfaces, activating the complement cascade and inducing necrotic cell death specifically in tumor cells.

Conclusions:

• AIM possesses potent anti-HCC activity by selectively targeting cancer cells for destruction.
• AIM deficiency exacerbates HCC development, particularly in the context of steatosis.
• These findings support the development of novel AIM-based therapeutic strategies for HCC.