TABLE 2.
Pro- and antiangiogenic their importance in the angiogenesis process.
| Angiogenic factors | Major function in angiogenesis process | References |
| Pro-angiogenic factors | ||
| VEGF-A, PlGF, VEGF-B, VEGF-C, VEGF-D, VEGF-E | Vasculature formation; Formation of primitive endothelial tubes; Induce proliferation, migration, and differentiation of EC | Kazemi et al., 2002 |
| aFGF, bFGF | Development and maintenance of a mature vascular network | Eguchi et al., 1992; Lee et al., 2000 |
| MMP-9; MMP-14 | Direct degradation of ECM proteins; overexpression of MMP-14 increases VEGF production and angiogenesis in glioblastomas | Deryugina and Quigley, 2015 |
| Angiogenin | Support endothelial survival and proliferation, endothelial tube development | Miyake et al., 2015 |
| FGF2, FGF5 | Induce cell sprouting elongated morphology with prominent filopodia; endothelial cell growth and movement | Seo et al., 2016 |
| TGFα/β, PDGF, TNFα, HGF/SF, COX-2 | Induce differentiation of EC, proliferation and migration | Yoo and Kwon, 2013 |
| NPAS4 | Regulates VE-cadherin expression and regulates sprouting angiogenesis and tip cell formation | Esser et al., 2015 |
| TBX3 | Its overexpression drives angiogenesis and tumor expansion in vivo | Krstic et al., 2020 |
| Nuclear factor 90 | Sustain tube formation and cell migration of HUVECs and expression of VEGF-A induced by hypoxia in cancer | Zhang et al., 2018 |
| TSLP | Promotes angiogenesis in cervical cancer | Zhou et al., 2017 |
| TXNDC5 | Down-regulate SERPINF1 and TRAF1 expression; sustain atypical angiogenesis, vasculogenic mimicry and metastasis | Xu et al., 2017 |
| IL-1, IL-5, IL-6, IL-8, IL-17 | Pro-inflammatory chemokines secreted by leukocytes and macrophages. Induce endothelial cell tube formation and vascularization | Ribatti, 2018 |
| LAPTM4B | Promote tumor angiogenesis through the HIF-1α and VEGF pathway | Meng et al., 2015 |
| CD146 | New coreceptor for VEGFR-2; EMT inducer; promotes endothelial cell migration and angiogenesis and human tumor growth | Jiang et al., 2012 |
| Anti-angiogenic factors | ||
| Angiopoietin: ANG-1 ANG-2 | Stabilization of existing vessels, control the interaction between ECs and the surrounding environment; ANG-1 suppresses ICAM-1, VCAM-1 and E-selectin; ANG-2 is an antagonist for ANG-1 and inhibits blood vessels maturation | Huang and Bao, 2003 |
| TSP-1, TSP-2 | Suppresses migration and induces endothelial cell apoptosis by blocking angiogenic factor access to co-receptors on the endothelial cell surface | Huang and Bao, 2003 |
| TIMP1 | Inhibit MMP9 or uPA activity; binds to MMP-9 to inhibit its active form | Yabluchanskiy et al., 2013 |
| Angiostatin | Directly inhibit neutrophil migration and neutrophil-mediated angiogenesis | Benelli et al., 2002 |
| Endostatin | Inhibition of ECs proliferation and migration, tube formation | Ergün et al., 2010 |
| Vasostatin | Angiogenesis inhibitor that specifically targets proliferating ECs | Pike et al., 1998 |
| Interferon-alpha | IFN α – decrease VEGF gene expression | von Marschall et al., 2003 |
| Interleukins: IL-1β, IL-4, IL-10, IL-12, IL-18, IL-23, IL-25, IL-27 | Inhibits endothelial cell proliferation | Ribatti, 2018 |
| TGF -beta | Suppresses VEGFA-mediated angiogenesis and tumor progression and metastasis | Geng et al., 2013 |
| SEMA3A | Endogenous inhibitor expressed in premalignant lesions that disappear during tumor progression. | Maione et al., 2009 |
Cox-2, cyclooxygenase-2; PlGF, placental growth factor; NPAS4, neuronal PAS domain protein 4; TBX3, T-box transcription factor 3; HGF/SF, hepatocyte growth factor/scatter factor; TSLP, thymic stromal lymphopoietin; TXNDC5, thioredoxin domain-containing protein 5; CD146, cluster of differentiation 146; ANG, angiopoietin; ICAM-1, intercellular adhesion molecule-1; VCAM-1, vascular cell adhesion molecule-1; TSP, thrombospondin; TIMP1, TIMP metallopeptidase inhibitor 1; SEMA3A, semaphorin 3A.