Multiple indirect angiogenesis-related pathways via paracrine mechanisms

Multiple indirect angiogenesis-related pathways via paracrine mechanisms refers to the physiological and pathological process where cells release signaling molecules to induce the formation of new blood vessels from pre-existing ones in a non-cell-autonomous manner (Carmeliet & Jain, 2011). This mechanism is primarily mediated by the secretion of growth factors such as Vascular Endothelial Growth Factor (VEGF), Basic Fibroblast Growth Factor (bFGF), and Transforming Growth Factor-beta (TGF-β), which travel through the interstitial space to bind receptors on nearby endothelial cells (Potente et al., 2011). These interactions trigger complex intracellular signaling cascades, including the Notch and Wnt pathways, which coordinate the sprouting of endothelial cells and the recruitment of pericytes for vessel stabilization (Hanahan & Weinberg, 2011). In oncology, tumors utilize these paracrine pathways to overcome hypoxia and sustain growth, making them a primary focus for anti-angiogenic therapies (Kerbel, 2008). Conversely, in regenerative medicine, therapeutic strategies aim to harness these paracrine effects to treat ischemic diseases by promoting revascularization (Gnecchi et al., 2008). Because this term describes a broad set of pathways and interactions rather than a single molecular entity, it is classified as a biological mechanism rather than a discrete therapeutic target. Therapeutic agents like Bevacizumab or multi-kinase inhibitors target specific nodes within these pathways to disrupt the overall paracrine signaling network (Jayson et al., 2016).

Other names

Paracrine angiogenic signalingIndirect pro-angiogenic signalingTumor-induced paracrine angiogenesisParacrine-mediated neovascularization

Inhibition of secreted pro-angiogenic ligands or their cognate receptors to disrupt paracrine signaling between source cells (e.g., tumor cells) and target endothelial cells.