Integrin and cell adhesion receptor (CAM)

Integrins and adhesion receptors are a diverse group of transmembrane glycoproteins that mediate essential interactions between cells and their environment, including the extracellular matrix (ECM) and neighboring cells. Integrins, which function as alpha-beta heterodimers, are the most prominent members and are unique for their ability to perform bidirectional signaling, translating external mechanical cues into internal biochemical signals and vice versa (Hynes, 2002, Cell). Other major classes include cadherins, which facilitate calcium-dependent cell-cell adhesion; selectins, which mediate the initial rolling of leukocytes on vascular endothelium; and the immunoglobulin superfamily (IgSF), such as ICAM-1 and VCAM-1, which provide stable docking for immune cells (Ley et al., 2007, Nat Rev Immunology). These receptors are fundamental to physiological processes like tissue morphogenesis, wound healing, and immune surveillance. In disease states, their dysregulation is a hallmark of cancer progression, where they facilitate tumor cell invasion and survival, as well as chronic inflammatory conditions like Crohn's disease and multiple sclerosis (Desgrosellier & Cheresh, 2010, Nat Rev Cancer). Pharmacological targeting of these receptors has led to the development of several blockbuster drugs, including integrin antagonists that prevent thrombosis by inhibiting platelet aggregation or treat autoimmune diseases by blocking leukocyte trafficking to specific tissues (Kapp et al., 2017, Expert Opin Ther Pat).

Other names

Cell adhesion moleculesCAMsAdhesion receptorsIntegrin familyAdhesion molecules

Drugs targeting these receptors primarily act as competitive antagonists that block the binding of endogenous ligands to the receptor's active site. For example, anti-integrin antibodies or small molecules often target the RGD (Arg-Gly-Asp) or LDV (Leu-Asp-Val) binding pockets, preventing the receptor from interacting with extracellular matrix proteins like fibronectin or cell-surface counter-receptors like VCAM-1 and MAdCAM-1. This blockade inhibits cell-cell or cell-matrix adhesion, effectively disrupting leukocyte recruitment to inflammatory sites, preventing platelet aggregation, or interfering with tumor angiogenesis and metastasis.