Extracellular Matrix Modulation by Cancer-Derived Extracellular Vesicles: Impact on Cancer Malignancy

The tumor microenvironment (TME) is an intricate network that influences cancer progression, comprising cancer cells, stromal cells, immune cells, and the extracellular matrix (ECM). The ECM, a scaffold of macroproteins like collagens and proteoglycans, is critical for maintaining tissue structure and regulating cellular functions. It undergoes significant remodeling in cancer, affecting cell proliferation, invasion, and drug response. Recent studies highlight the role of extracellular vesicles (EVs), lipid bilayer vesicles carrying bioactive molecules, secreted by cancer cells in modulating the ECM. Cancer EVs modulate the ECM by stimulating cancer-associated fibroblasts (CAFs) and other stromal cells to produce ECM components and by directly altering ECM structure through enzymes they carry or by modulating cancer cell–ECM interactions. The altered ECM facilitates cancer progression by establishing pre-metastatic niches, enhancing tumor invasion, and affecting drug efficacy. This chapter summarizes the roles of cancer EVs in remodeling ECM in tumors, highlighting how EVs influence ECM secretion by stromal cells, directly modify ECM structures, and impact tumor traits and clinical outcomes. Understanding the interaction between EVs and the ECM in the TME is crucial for developing novel diagnostic and therapeutic strategies targeting EV-mediated ECM remodeling to disrupt the metastatic cascade and improve cancer treatment efficacy.