The specific contributions of various complement proteins to neoplastic phenomena
| Complement protein | Tumorigenic effect | Tumorigenic hallmark |
|---|---|---|
| C1q | Extracellular matrix anchoring | Invasion and migration |
| C1s | Extracellular matrix disintegration | Invasion and migration |
| Activation of MMP-9 | Invasion and migration | |
| C3 | Production of VEGF | Angiogenesis |
| Extracellular matrix reorganization | Invasion and migration | |
| Extracellular matrix disintegration | Invasion and migration | |
| C3a | Activation of ERK1/2, Akt | Mitogenesis |
| Induction of IL-6 | Growth factor/cytokine production | |
| Production of VEGF | Angiogenesis | |
| Extracellular matrix reorganization | Invasion and migration | |
| Cellular chemotaxis | Invasion and migration | |
| C3d | Extracellular matrix anchoring | Invasion and migration |
| Factor B | Extracellular matrix disintegration | Invasion and migration |
| C5 | Induction of TGF-β, IGFs, IGFBPs | Growth factor/cytokine production |
| Extracellular matrix disintegration | Invasion and migration | |
| C5a | Activation of ERK1/2, Akt, JNK, p38 MAPK, phospholipase C β-2, phospholipase D, MEK-1, PKC, NF-κB | Mitogenesis |
| Stimulation of HGF, c-MET receptor | Growth factor/cytokine production | |
| Transactivation of EGFR | Mitogenesis, cellular migration | |
| Induction of cyclin E, D1 | Mitogenesis | |
| Induction of IL-6 | Growth factor/cytokine production | |
| Inhibition of caspase-3 | Prevention of apoptosis | |
| Production of VEGF | Angiogenesis | |
| Cellular chemotaxis | Invasion and migration | |
| Inhibition of CD8+ T cells | Antitumor Immunosuppression | |
| MDSC migration and production of ROS/RNS | Antitumor immunosuppression | |
| C9 | Extracellular matrix disintegration | Invasion and migration |
| MAC | Induction of CDK 2 and 4, p21, RGC-32 | Mitogenesis |
| Activation of ERK, p38 MAPK, JNK, PI3K, Ras, p70 S6 kinase, JAK-STAT | Mitogenesis | |
| Activation of c-jun, junD, c-fos | Mitogenesis | |
| Induction of bFGF, PDGF, TGF-β | Growth factor/cytokine production, angiogenesis | |
| Inhibition of caspase-3, caspase-8, BAD, BID, TNF-α, FasL | Prevention of apoptosis | |
| Induction of bcl-2, IGF-I | Prevention of apoptosis | |
| Production of VEGF | Angiogenesis |
Abbreviations: BAD, bcl-xL/bcl-2–associated death promoter; Bcl-2, B-cell lymphoma-2; bFGF, basic fibroblast growth factor; BID, bcl-2 interacting domain; CDK, cyclin-dependent kinase; EGFR, epidermal growth factor receptor; ERK, extracellular signal-regulated kinase; FasL, Fas ligand; HGF, hepatocyte growth factor; IGF, insulin-like growth factor; IGFBP, insulin-like growth factor binding protein; IL-6, interleukin-6; JAK-STAT, Janus activated kinase–signal transducer and activated transcription; JNK, c-jun amino terminal kinase; MAPK, mitogen-activated protein kinase; MDSC, myeloid-derived suppressor cells; MEK-1, mitogen-activated protein kinase or ERK kinase-1; METr, mesenchymal-epithelial transition receptor; MMP-9, matrix metalloproteinase 9; PI3K, phosphatidylinositol 3-kinase; PDGF, platelet-derived growth factor; PKC, protein kinase C; RGC, response gene to complement; ROS/RNS, reactive oxygen species/reactive nitrogen species; TGF-β, transforming growth factor-β; TNF-α, tumor necrosis factor-α; VEGF, vascular endothelial growth factor.