Message in the bottle: regulation of the tumor microenvironment via exosome-driven proteolysis

Abstract

Exosomes comprise a subtype of extracellular vesicles involved in cell-to-cell communication, specifically by transporting biological molecules, such as proteins and nucleic acids, to either local or more distant recipient cells, thus triggering distinct biological behaviours. Included in the exosome cargo is frequently a wide range of proteolytic enzymes, such as the matrix metalloproteinases (MMPs), the disintegrin and metalloproteinases (ADAMs), and the ADAM with thrombospondin-like motifs (ADAMTSs), whose functions contribute to the development and progression of cancer. In recent years, extensive research on the potential use of exosomes in diagnostic and therapeutic applications for personalized medicine has emerged, but the targeting of the proteolytic cargo of exosomes has not been fully exploited in this direction. In this review, we aim to explore both the mechanistic and the translational importance of proteolytic enzymes carried by the tumour-cell derived exosomes, as well as their role in the acquisition and support of certain hallmarks of cancer.

Exosomal Cargo in Ovarian Cancer Dissemination

“…The extensive use of transmission electron microscopy (TEM) has confirmed that exosomes are extracellular vesicles (EVs) characterized by low electron density and a cupshaped morphology [36,37] in both the plasma and ascites of the OC patients (Figure 2). Additionally, cryo-electron microscopy has identified subpopulations of exosomes with single-, double-, and multi-layer membranes [36,38,39].…”

Crosstalk between colorectal cancer cells and cancer-associated fibroblasts in the tumor microenvironment mediated by exosomal noncoding RNAs

“…The Endosomal sorting complex required for transports (ESCRT) is involved in classical exosome formation. The ESCRT complex can be broadly divided into four components of ESCRT0, ESCRTTI, ESCRTII and ECRTIII (78)(79)(80). During the biogenesis of MVBs, the cellular material to be transported is ubiquitinated and the ESCRT0 complex is recruited to the membrane of the secretory endosome.…”

ADAMTS Proteases: Their Multifaceted Role in the Regulation of Cancer Metastasis

“…The function of matrix-metalloproteinases (MMPs) and A disintegrin and metalloproteinases (ADAMs) has been extensively characterised in tumorigenesis. Indeed, dysregulation of these proteases was found to promote tumour progression by supporting ECM remodelling, angiogenesis, cancer cell migration and invasion, and disruption of cancer-associated immune reactions [ 2 , 3 ] . Since these proteases have been found relevant to the progression of several types of cancer, they were considered as potential targets for cancer diagnosis and therapy.…”