An update on the role of complement in hepatocellular carcinoma

Abstract

As a main producer of complement, the environment in the liver is greatly affected by the complement system. Although the complement system is considered to have the ability of nonself discrimination, remarkable studies have revealed the tight association between improper complement activation in tumour initiation and progression. As complement activation predominantly occurs within the liver, the protumourigenic role of the complement system may contribute to the development of hepatocellular carcinoma (HCC). Improvement in the understanding of the molecular targets involved in complement-mediated tumour development, metastasis, and tumour-promoting inflammation in HCC would certainly aid in the development of better treatments. This minireview is focused on recent findings of the protumourigenic role of the complement system in HCC.

Keywords: complement; hepatocellular carcinoma; metastasis; stemness; tumour microenvironment; tumourigenesis.

Figure 1

The complement cascade at a glance. The complement cascade can be activated by three pathways, (1) The classical pathway, (2) the lectin pathway and (3) the alternative pathway. Initiation of all three pathways can lead to the formation of C5 convertase to produce C5b, which then recruit C6, C7, C8 and C9 molecules. Together these components can form the terminal membrane attack complex (MAC), which induce cell lysis by inserting pores in cell membranes.

Figure 2

An overview of the complement activation in HCC tumour microenvironment. Tumour cells are capable of hijacking the immune system to cultivate a favourable TME. Different components of the complement pathway were found to be triggered and modified, forming an immunosuppressive environment. The schematic illustration summarised intricate interactions between tumour cells and the complement system, which promotes HCC tumourigenesis, metastatic and stemness.