Paracrine ligand–receptor network

A paracrine ligand–receptor network refers to a fundamental mode of cell-to-cell communication where a cell produces a signal (ligand) to induce changes in nearby cells, altering the behavior or differentiation of those cells (Nature, 2023). Unlike endocrine signaling, which uses the circulatory system to transport ligands over long distances, paracrine signals diffuse through the extracellular matrix to act locally (NIH, 2022). This network is composed of diverse molecular families, including growth factors, cytokines, and neurotransmitters, along with their cognate receptors such as receptor tyrosine kinases and G protein-coupled receptors. These interactions are critical for maintaining tissue homeostasis, coordinating immune responses, and guiding embryonic development. In many diseases, particularly cancer, these networks are dysregulated; for instance, tumor cells may hijack paracrine signaling to recruit stromal cells or promote angiogenesis (PubMed, 2021). While the network itself is not a single therapeutic target, its individual components are frequently targeted by monoclonal antibodies and small molecule inhibitors to disrupt pathological signaling loops. Therapeutic strategies often focus on blocking the ligand-receptor interface or inhibiting the downstream intracellular signaling cascades initiated by these local interactions. Understanding the spatial and temporal dynamics of these networks is essential for developing precision medicines that can selectively modulate local environments without systemic toxicity.

Other names

Paracrine signalingLocal cell-cell communicationParacrine loopLocal signaling network

Antagonism of specific ligands or receptors to disrupt local signaling loops within the tissue microenvironment.