Angiocrine signaling and endothelial niche

Angiocrine signaling and direct cell-cell contact describe the complex regulatory mechanisms by which endothelial cells (ECs) instruct the behavior of surrounding parenchymal and stem cells. Rather than acting as simple blood conduits, ECs secrete a variety of organ-specific growth factors, cytokines, and extracellular matrix components—collectively known as angiocrine factors—that are vital for tissue development and regeneration (Rafii et al., 2016). Direct cell-cell contact, or juxtacrine signaling, involves membrane-bound ligands such as Notch (e.g., DLL4) and Ephrins that provide spatial cues to neighboring cells (Butler et al., 2010). This vascular niche is essential for maintaining the stem cell pool in organs like the bone marrow and liver. In diseases like cancer, the vascular niche is often co-opted to support tumor growth, promote metastasis, and protect malignant cells from chemotherapy. Conversely, in chronic organ injury, the loss of proper angiocrine signaling can lead to maladaptive repair and the development of fibrosis. Therapeutic interventions targeting this system focus on specific molecular components, such as VEGF or Notch ligands, to either inhibit pathological niches or stimulate regenerative ones. Drugs like bevacizumab and demcizumab are examples of agents that modulate these pathways to treat cancer (Poulos et al., 2017).

Other names

Vascular niche signalingEndothelial-derived paracrine signalingAngiocrine systemJuxtacrine endothelial signalingEndothelial-cell-contact-mediated niche

Modulation of endothelial-secreted growth factors (angiocrine factors) and membrane-bound ligands to regulate parenchymal cell behavior, tissue repair, and the tumor microenvironment.