Molecular pathways underlying angiogenesis. Molecular pathways underlying angiogenesis. A: Tumour cells produce vascular endothelial growth factor (VEGF)-A and other angiogenic factors, such as basic fibroblast growth factor (bFGF), angiopoietins, interleukin-8, placental growth factor and VEGF-C. These stimulate resident endothelial cells to proliferate and migrate. B: An additional source of angiogenic factors is the stroma. This is a heterogeneous compartment, comprising fibroblastic, inflammatory and immune cells. Recent studies indicate that tumour-associated fibroblasts produce chemokines, such as stromal cell-derived factor (SDF)-1, which may recruit bone-marrow-derived angiogenic cells (BMC). VEGF-A or placental growth factor may also recruit BMC. Tumour cells may also release stromal cell-recruitment factors, such as platelet-derived growth factor (PDGF)-A, PDGF-C or transforming growth factor (TGF)-β. A well-established function of tumour-associated fibroblasts is the production of growth/survival factor for tumour cells, such as epidermal growth factor (EGF) receptor ligands, hepatocyte growth factor and heregulin. C: Endothelial cells produce PDGF-B, which promotes recruitment of pericytes in the microvasculature after activation of PDGF receptor-β. HGF: hepatocyte growth factor. Reproduced from [10] with permission. Lucio Crinò, and Giulio Metro Eur Respir Rev 2014;23:79-91 ©2014 by European Respiratory Society