Exosome mediated crosstalk in gastrointestinal cancers progression: special focus on Integrin β3 as a cargo

Intercellular communication within the tumor microenvironment (TME) is highly active in gastrointestinal (GI) cancers, and exosomes have an important function in tumor development, progression, metastasis, angiogenesis, and drug resistance. Exosomes secreted by tumor cells actively remodel their local environment by delivering oncogenic proteins, genetic material, and integrins, contributing to processes such as invasion, immune escape, and metastatic niche formation. Cancer-associated fibroblasts (CAFs) are a main source of exosomes in the stroma, and their presence boosts tumor progression by orchestrating changes in the extracellular matrix composition, metabolism, and epithelial to mesenchymal transition. Similarly, exosomes produced by endothelial cells facilitate angiogenesis and increase vascular permeability, providing a mechanism for tumor spread. One of the key factors recently discovered in exosomes is the integrin β3, which plays a major role in organotropic metastasis, cell adhesion, migration, and activation of signaling pathways in GI cancers. In this review, the biological roles of exosomes isolated from tumors, CAFs, and endothelial cells have been highlighted, especially with reference to the functional significance of integrin β3 in GI cancers. This review also provides insight into the application of integrin β3 in exosomes as a biomarker for early detection, diagnosis, and treatment. The knowledge gained through exosome-based signaling could lead to new approaches for interfering with TME-associated tumor progression.