Abstract
Integrins represent the biologically and medically significant family of cell adhesion molecules that govern a wide range of normal physiology. The activities of integrins in cells are dynamically controlled via activation-dependent conformational changes regulated by the balance of intracellular activators, such as talin and kindlin, and inactivators, such as Shank-associated RH domain interactor (SHARPIN) and integrin cytoplasmic domain-associated protein 1 (ICAP-1). The activities of integrins are alternatively controlled by homotypic lateral association with themselves to induce integrin clustering and/or by heterotypic lateral engagement with tetraspanin and syndecan in the same cells to modulate integrin adhesiveness. It has recently emerged that integrins are expressed not only in cells but also in exosomes, important entities of extracellular vesicles secreted from cells. Exosomal integrins have received considerable attention in recent years, and they are clearly involved in determining the tissue distribution of exosomes, forming premetastatic niches, supporting internalization of exosomes by target cells and mediating exosome-mediated transfer of the membrane proteins and associated kinases to target cells. A growing body of evidence shows that tumor and immune cell exosomes have the ability to alter endothelial characteristics (proliferation, migration) and gene expression, some of these effects being facilitated by vesicle-bound integrins. As endothelial metabolism is now thought to play a key role in tumor angiogenesis, we also discuss how tumor cells and their exosomes pleiotropically modulate endothelial functions in the tumor microenvironment.
Highlights
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations
This study demonstrated in vivo that naïve macrophage exosomes can cross the blood–brain barrier and ferry a cargo protein, brain-derived neurotrophic factor (BDNF), to the brain parenchyma, especially under inflammatory conditions [116]
It was shown that the binding of rat adenocarcinoma cell-derived exosomes to endothelial cells and subsequent internalization depend on the vesicular expression of the Tspan8integrin α4 complex [110]
Summary
Integrins are cell adhesion receptors whose proper functioning plays a very significant role in diverse physiologic processes, such as embryonic development, cell proliferation, leukocyte adhesion and platelet aggregation [1]. Integrins constitute the integral components of the plasma membrane, thereby integrating the extracellular and intracellular events of a living cell and transmitting the cellular signals bidirectionally [2]. We discuss the general activation mechanism of integrins in cells. We describe the integrin-regulation mechanism in exosomes, as well as the biological functions and significance of exosomes derived from immunological and cancerous cells. As these exosomes modulate the behavior, metabolism and functions of endothelial cells, we elucidate their role in tumor angiogenesis
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have