Components of the Lectin Pathway of Complement in Solid Tumour Cancers

Abstract

The complement system is an important branch of the humoral innate immune response that can be activated via three distinct pathways (classical, alternative, lectin), contributing to keeping/restoring homeostasis. It can also interact with cellular innate immunity and with components of acquired immunity. Cross-talk between the complement system and other enzyme-dependent cascades makes it a more influential defence system, but on the other hand, over- or chronic activation can be harmful. This short review is focused on the dual role of the lectin pathway of complement activation in human solid tumour cancers, including those of the female reproductive system, lung, and alimentary tract, with emphasis on the aforementioned cross-talk.

Keywords: MBL-associated serine protease (MASP); cancer; collectin; complement; ficolin; lectin pathway.

Figure 1

Activation of complement via the lectin pathway and its cross-talk with other processes. MASP-1 participates in the coagulation/fibrinolysis cascade via activation of prothrombin and factor XIII, and cleavage of thrombin-activatable fibrinolysis inhibitor (TAFI). It furthermore interacts with protease-activated receptor 4 (PAR4). MASP-1 cleaves high molecular weight kininogen as well, resulting in release of bradykinin, thus cross-talking with the kallikrein–kinin system. MASP-2 activates prothrombin (coagulation pathway), while MASP-3 activates pro-factor D (cross-talk with alternative pathway of complement). As mentioned within the main text, LP shares C3 and C5 convertases with the classical pathway. PRM—pattern-recognizing molecule (collectin or ficolin); HMWK—high molecular weight kininogen.

Figure 2

Multifaceted associations of complement with cancer. (Left panel)—effects beneficial for the host: complement activation leads to direct lysis of cancer cells (via formation of C5b9 complex; complement-dependent cytotoxicity, CDC), contributes to complement-dependent cellular cytotoxicity (CDCC) and phagocytosis (via opsonization of cancer cells with activated compounds), enhances the effect of antibodies (including therapeutic) (contribution to antibody-dependent cellular cytotoxicity, ADCC), and elimination of apoptotic/necrotic cells and some oncogenic pathogens. (Right panel)—effects detrimental for the host (mediated predominantly but not only by anaphylatoxins and/or formation of C5b9 complex): chronic inflammation may promote neoplastic transformation, uncontrolled complement activation may contribute to promotion of tumour cell proliferation/migration/invasiveness, angiogenesis, production of growth factors, and suppression of host response (especially via C5a action on myeloid-derived suppressor cells, which contributes to the decrease of CD8+ lymphocytes mediated by reactive nitrogen/oxygen species).