Extracellular vesicles: biological packages that modulate tumor cell invasion

Tumor progression, from early-stage invasion to the formation of distal metastases, relies on the capacity of tumor cells to modify the extracellular matrix (ECM) and communicate with the surrounding stroma. Extracellular vesicles (EVs) provide an important means to regulate cell invasion due to the selective inclusion of cargoes such as proteases and matrix proteins into EVs that can degrade or modify the ECM. EVs have also been shown to facilitate intercellular communication in the tumor microenvironment through paracrine signaling, which can impact ECM invasion by cancer cells.

Researchers from the University of Notre Dame describe the current knowledge of EVs as facilitators of tumor invasion by virtue of their effects on proteolytic degradation and modification of the ECM, their ability to educate the stromal cells in the tumor microenvironment, and their role as mediators of long-range communication aiding in cell invasion and matrix remodeling at secondary sites.

Extracellular vesicles (EVs) shed from cells facilitate invasion
of the extracellular matrix (ECM) in many ways

Tumor cells may toggle between amoeboid and mesenchymal phenotypes and shed EVs that contain proteases such as MMPs and heparinase, as well as ECM components like fibronectin, allowing for matrix remodeling and cell invasion. Highly aggressive tumor cell lines adopt amoeboid morphologies and release larger-sized ectosomes to facilitate degradation. Exosomes are secreted at invadopodia on the adherent surface of tumor cells to aid in proteolytic degradation of the ECM. EVs can deposit ECM components that affect matrix composition and stiffening. Shed EVs may also activate stromal cells such as fibroblasts and inform behaviors that advance tumorigenesis. In response to EV uptake, fibroblasts increase collagen compaction and provide tracks for leader–follower pathfinding behaviors during matrix invasion. EV uptake also results in an increase in fibronectin production by fibroblasts.

Schmidtmann M, D’Souza-Schorey D. (2023) Extracellular Vesicles: Biological Packages That Modulate Tumor Cell Invasion. Cancers 15(23), 5617. [article]

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