The Role of Exosomal Tetraspanins and Proteases in Tumor Progression

Major (CD9, CD63, CD81) and other (CD82, CD151, Tspan8) exosomal tetraspanins interact with various proteins and form functional tetraspanin complexes in exosomes. The tetraspanin complexes contain various proteins including proteases. Tetraspanin-associated exosomal proteases (ADAM proteases, MMPs, EMMPRIN) play an important role in cell motility, migration, invasion and formation of metastases. Proteases that are not associated with tetraspanins also significantly contribute to tumor progression. They destabilize intercellular contacts, promote migration and invasion of tumor cells, and participate in regulation of the expression IGF-I, VEGF, and the activated forms of transcription factors. The role of other exosomal proteases in tumor progression is being clarified.