Abstract
The complement system is part of the body's innate defense immune system, which can identify and eliminate invasive pathogenic microorganisms to maintain normal life activities. Complement Component 5a (C5a) is an active anaphylatoxin produced after complement system activation, closely related to tumor formation. C5a is highly expressed in a variety of tumors, and combines with its Complement Component 5a Receptor (C5aR) to increase the proliferation and migration of tumor cells. This review will comprehensively elaborate the important role of C5a/C5aR in the process of tumor genesis and development from the three aspects of signal transduction pathways related to tumor, C5a/C5aR and tumor formation, and C5a/C5aR inhibitors and tumor therapy. Finally, the principle of complement inhibition is used to inhibit tumor metastasis, reduce the rate of tumor diffusion, and control the trend of tumor deterioration.
Highlights
The generation of tumor is closely related to the microenvironment in which tumor is located
It plays the role of chemokines in the immune response to infectious diseases, and promotes the migration of white blood cells and the production of oxygen free radical by combining with the G protein-coupled receptors C5aR1 and C5aR2 expressed on the white cell membrane, triggering the inflammatory response[8]
The injection of Component 5a (C5a) into cells pretreated with PI3K inhibitors blocked this inhibitory effect. These results showed that the C5a/Component 5a Receptor (C5aR) pathway inhibited the expression of p21/p-p21 by activating the PI3K/AKT signaling pathway, thereby promoting the incidence of gastric cancer[11]
Summary
The generation of tumor is closely related to the microenvironment in which tumor is located. Complement activation occurs through three main interaction pathways: the classical pathway, the alternative pathway, and the lectin pathway These pathways have different initiation mechanisms but converge in the formation of C5 convertases which catalyze the cleavage of C5 into C5a and C5b, and assembles the membrane attack complex (MAC) to cleave the target protein[4] (Figure 1). C5a is a potent anaphylatoxin, which is highly expressed in neutrophils, macrophages, dendritic cells and non-immune cells[7] It plays the role of chemokines in the immune response to infectious diseases, and promotes the migration of white blood cells and the production of oxygen free radical by combining with the G protein-coupled receptors C5aR1 and C5aR2 expressed on the white cell membrane, triggering the inflammatory response[8]. We listed several representative treatment strategies for C5a/C5aR related diseases, summarized the methods to treat cancer by inhibiting C5a/C5aR, and made a reasonable prospect for the future application and development of complement system in the field of tumor therapy
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