title: Complement and macrophage crosstalk during process of angiogenesis in tumor progression.
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.
authors.affiliation: Department Comparative Medicine, King Faisal Specialist Hospital and Research Centre, MBC 03, P.O. Box 3354, Riyadh, 11211, Kingdom of Saudi Arabia. mkhan26@kfshrc.edu.sa.
authors.forename: M Afzal
authors.initials: MA
authors.lastname: Khan
authors.affiliation: Department Comparative Medicine, King Faisal Specialist Hospital and Research Centre, MBC 03, P.O. Box 3354, Riyadh, 11211, Kingdom of Saudi Arabia.
authors.forename: A M
authors.initials: AM
authors.lastname: Assiri
authors.affiliation: Organ Transplant Centre, King Faisal Specialist Hospital and Research Centre, Riyadh, Kingdom of Saudi Arabia.
authors.forename: D C
authors.initials: DC
authors.lastname: Broering
mesh_terms: D000818:Animals; D015926:Complement C3a / Q000378:metabolism*; D015936:Complement C5a / Q000378:metabolism*; D006801:Humans; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000378:metabolism* / Q000473:pathology
chemical_list: D015926:Complement C3a; D015936:Complement C5a