A role of tumor-released exosomes in paracrine dissemination and metastasis

E.P. Spugnini, M. Logozzi, R. Di Raimo, D. Mizzoni, S. Fais

Research output: Contribution to journalArticlepeer-review


Metastatic diffusion is thought to be a multi-step phenomenon involving the release of cells from the primary tumor and their diffusion through the body. Currently, several hypotheses have been put forward in order to explain the origin of cancer metastasis, including epithelial–mesenchymal transition, mutagenesis of stem cells, and a facilitating role of macrophages, involving, for example, transformation or fusion hybridization with neoplastic cells. In this paradigm, tumor-secreted extracellular vesicles (EVs), such as exosomes, play a pivotal role in cell communications, delivering a plethora of biomolecules including proteins, lipids, and nucleic acids. For their natural role in shuttling molecules, EVs have been newly considered a part of the metastatic cascade. They have a prominent role in preparing the so-called “tumor niches” in target organs. However, recent evidence has pointed out an even more interesting role of tumor EVs, consisting in their ability to induce malignant transformation in resident mesenchymal stem cells. All in all, in this review, we discuss the multiple involvements of EVs in the metastatic cascade, and how we can exploit and manipulate EVs in order to reduce the metastatic spread of malignant tumors. © 2018 by the authors. Licensee MDPI, Basel, Switzerland.
Original languageEnglish
JournalInternational Journal of Molecular Sciences
Issue number12
Publication statusPublished - 2018


  • Cell-free DNA
  • Exosomes
  • Extracellular vesicles
  • Metastasis
  • Metastatic niche
  • Tumor microenvironment
  • microRNA
  • small interfering RNA
  • vasculotropin
  • apoptosis
  • carcinogenesis
  • cardiovascular disease
  • enzyme linked immunosorbent assay
  • human
  • hypoxia
  • immune response
  • liquid biopsy
  • nonhuman
  • oxidative stress
  • paracrine signaling
  • pleura effusion
  • Review
  • tumor growth
  • tumor microenvironment


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