Angiogenesis in gastrointestinal stromal tumors: From bench to bedside

Table 1 The basic mechanisms of angiogenesis

Angiogenetic mechanism	Function	Implicated signaling/ pathways
Sprouting angiogenesis	Vessel formation from a parental one as a sprout outgrowth	VEGF, Dll4/notch pathways and neuropilins
Intussusceptive Angiogenesis	Splitting of a parental vessel into two newly formed	VEGF, PDGF pathways and erythropoietin
Vasculogenesis/Endothelial progenitor cells	Vessel formation from endothelial progenitor cells differentiating into mature endothelial cells	VEGF pathway, chemokines
Vasculogenic mimicry	Vessel-like formations without endothelial cells	HGFR
Trans-differentiation of CSCs	CSC give rise to endothelial cells	Tie-2, TGF-, CXCL12/CXCR4

PDGF-R: Platelet-derived growth factor receptor; VEGF: Vascular endothelial growth factor; HGFR: Hepatocyte growth factor receptor; TGF-: Transforming growth factor-; CSCs: Cancer stem cells, CXCL12: C-x-c motif chemokine ligand 12; CXCR4: C-x-c motif chemokine receptor 4.