Abstract
The complement system, which contains some of the most potent pro-inflammatory mediators in the tissue including the anaphylatoxins C3a and C5a are the vital parts of innate immunity. Complement activation seems to play a more critical role in tumor development, but little attention has been given to the angiogenic balance of the activated complement mediators and macrophage polarization during tumor progression. The tumor growth mainly supported by the infiltration of M2- tumor-associated macrophages, and high levels of C3a and C5a, whereas M1-macrophages contribute to immune-mediated tumor suppression. Macrophages express a cognate receptors for both C3a and C5a on their cell surface, and specific binding of C3a and C5a affects the functional modulation and angiogenic properties. Activation of complement mediators induce angiogenesis, favors an immunosuppressive microenvironment, and activate cancer-associated signaling pathways to assist chronic inflammation. In this review manuscript, we highlighted the specific roles of complement activation and macrophage polarization during uncontrolled angiogenesis in tumor progression, and therefore blocking of complement mediators would be an alternative therapeutic option for treating cancer.
Highlights
The complement system has been primarily considered as an effector of innate immunity with the ability to antibody-mediated disposal of foreign particles, apoptotic clearance, and actively maintain the phase of immune surveillance in different inflammatory states [1,2,3,4]
The complement system help innate immune attack against cancer cells through cytotoxic and lytic effects but number of studies are revealing that the complement cascade enables a remarkable array of proliferative events [20]
M2 macrophages acts as a tumor promoters at distinct phases of malignant progression of gastric, mammary [97], lung [98], and liver carcinomas [99]
Summary
The complement system has been primarily considered as an effector of innate immunity with the ability to antibody-mediated disposal of foreign particles, apoptotic clearance, and actively maintain the phase of immune surveillance in different inflammatory states [1,2,3,4]. The complement activation play a dual role in tumor development, and it has been reported that it can control tumor activities through acute inflammation, immunostimulation, lysis, opsonization and chemotaxis [5]. The complement activation support chronic inflammation, promote an immunosuppressive microenvironment, induce angiogenesis, and activate cancer-related signaling pathways during tumor progression [6]. Khan et al Journal of Biomedical Science (2015) 22:58 cancer cells manipulates complement mechanism to protect their proliferation, and survival by recruiting tumor-associated macrophages (TAMs) and facilitates tumor progression
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