Cell-surface adhesion receptors and integrins mediating extracellular vesicle uptake

Cell-surface adhesion receptors and integrins mediating extracellular vesicle (EV) uptake are a functional group of transmembrane proteins that facilitate the docking and internalization of EVs, such as exosomes and microvesicles, by recipient cells. This group primarily includes various integrin heterodimers (e.g., αvβ3, α6β4, α4β1) and adhesion molecules like ICAM-1 and VCAM-1, which recognize ligands on the EV surface or bridging matrix proteins like fibronectin and laminin (NIH, 2025; Isogai et al., 2025). These interactions are essential for the selective binding of EVs and the subsequent activation of endocytic pathways, including clathrin-mediated endocytosis, macropinocytosis, and phagocytosis (Fuentes et al., 2021). By mediating the transfer of bioactive cargo such as miRNAs, proteins, and lipids, these receptors play a pivotal role in intercellular communication and the modulation of recipient cell phenotypes. In diseases like cancer, these receptors are exploited to promote metastasis, angiogenesis, and the establishment of pre-metastatic niches (Sese et al., 2017). Therapeutic targeting of these receptors using monoclonal antibodies, RGD-mimetic small molecules, or decoy peptides aims to disrupt pathological EV-mediated signaling. However, challenges remain due to the ubiquitous nature of these receptors in normal physiological processes like wound healing and immune response (Frontiers in Oncology, 2024). Additionally, the redundancy of integrin functions and the potential for off-target effects on non-pathological EVs complicate the development of specific inhibitors.

Other names

EV-uptake receptorsExosome receptorsIntegrin adhesion complexesIACsAdhesion molecules for EV internalization

Inhibition of extracellular vesicle (EV) uptake by blocking the interaction between EV surface ligands and recipient cell receptors, or by disrupting the endocytic machinery required for internalization.