Table 1.

The specific contributions of various complement proteins to neoplastic phenomena

Complement proteinTumorigenic effectTumorigenic hallmark
C1qExtracellular matrix anchoringInvasion and migration
C1sExtracellular matrix disintegrationInvasion and migration
Activation of MMP-9Invasion and migration
C3Production of VEGFAngiogenesis
Extracellular matrix reorganizationInvasion and migration
Extracellular matrix disintegrationInvasion and migration
C3aActivation of ERK1/2, AktMitogenesis
Induction of IL-6Growth factor/cytokine production
Production of VEGFAngiogenesis
Extracellular matrix reorganizationInvasion and migration
Cellular chemotaxisInvasion and migration
C3dExtracellular matrix anchoringInvasion and migration
Factor BExtracellular matrix disintegrationInvasion and migration
C5Induction of TGF-β, IGFs, IGFBPsGrowth factor/cytokine production
Extracellular matrix disintegrationInvasion and migration
C5aActivation of ERK1/2, Akt, JNK, p38 MAPK, phospholipase C β-2, phospholipase D, MEK-1, PKC, NF-κBMitogenesis
Stimulation of HGF, c-MET receptorGrowth factor/cytokine production
Transactivation of EGFRMitogenesis, cellular migration
Induction of cyclin E, D1Mitogenesis
Induction of IL-6Growth factor/cytokine production
Inhibition of caspase-3Prevention of apoptosis
Production of VEGFAngiogenesis
Cellular chemotaxisInvasion and migration
Inhibition of CD8+ T cellsAntitumor Immunosuppression
MDSC migration and production of ROS/RNSAntitumor immunosuppression
C9Extracellular matrix disintegrationInvasion and migration
MACInduction of CDK 2 and 4, p21, RGC-32Mitogenesis
Activation of ERK, p38 MAPK, JNK, PI3K, Ras, p70 S6 kinase, JAK-STATMitogenesis
Activation of c-jun, junD, c-fosMitogenesis
Induction of bFGF, PDGF, TGF-βGrowth factor/cytokine production, angiogenesis
Inhibition of caspase-3, caspase-8, BAD, BID, TNF-α, FasLPrevention of apoptosis
Induction of bcl-2, IGF-IPrevention of apoptosis
Production of VEGFAngiogenesis

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.