The Role of Cancer-Derived Exosomes in Tumorigenicity & Epithelial-to-Mesenchymal Transition

Abstract

Epithelial-to-mesenchymal transition (EMT) is a process by which epithelial cells lose their basement membrane interaction and acquire a more migratory, mesenchymal phenotype. EMT has been implicated in cancer cell progression, as cells transform and increase motility and invasiveness, induce angiogenesis, and metastasize. Exosomes are 30-100 nm membrane-bound vesicles that are formed and excreted by all cell types and released into the extracellular environment. Exosomal contents include DNA, mRNA, miRNA, as well as transmembrane- and membrane-bound proteins derived from their host cell contents. Exosomes are involved in intercellular signaling, both by membrane fusion to recipient cells with deposition of exosomal contents into the cytoplasm and by the binding of recipient cell membrane receptors. Recent work has implicated cancer-derived exosomes as an important mediator of intercellular signaling and EMT, with resultant transformation of cancer cells to a more aggressive phenotype, as well as the tropism of metastatic disease in specific cancer types with the establishment of the pre-metastatic niche.

Keywords: epithelial-mesenchymal transition; exosomes; intercellular signaling peptides and proteins; neoplasm invasiveness; neoplasm metastasis; neovascularization; pathologic.

Figure 1

Several mechanisms have been found for interaction and uptake of exosomes by target cells. Most well studied mechanisms are receptor-mediated exosomal uptake (endocytosis) (A), direct exosomal fusion with plasma membrane (B), and phagocytic exosomal uptake (phagocytosis) (C). Used with permission [20].

Figure 2

The role of cancer-derived exosomes in increasing tumorigenicity and epithelial-to-mesenchymal transition. Pathways associated with epithelial-to-mesenchymal transition are bolded.