Exosomes: Key mediators of metastasis and pre-metastatic niche formation

Abstract

While tumour cells are classically known to communicate via direct cell-to-cell contact and the secretion of soluble protein-based factors such as cytokines and growth factors, alternative novel mechanisms that promote tumour progression have recently emerged. Now, new critical components of the secretome thought to be involved in tumour progression are exosomes, small vesicles of endocytic origin that carry a variety of bioactive molecules, including proteins, lipids, RNA, as well as DNA molecules. Cancer cell-derived exosomes have been shown to participate in crucial steps of metastatic spread of a primary tumour, ranging from oncogenic reprogramming of malignant cells to formation of pre-metastatic niches. These effects are achieved through the mediation of intercellular cross-talk and subsequent modification of both local and distant microenvironments in an autocrine and paracrine fashion. Here, we summarise the recent findings that implicate this non-canonical signalling within the tumour as a critical driver of metastatic disease progression, and discuss how understanding the molecular mechanisms involved in exosome-mediated metastasis is of great value for the development of new therapeutic strategies to prevent cancer progression.

Hypoxia-induced exosomes contribute to a more aggressive and chemoresistant ovarian cancer phenotype: a novel mechanism linking STAT3/Rab proteins

“…Here, we observed that HEx has a similar effect on immortalized fallopian tube secretor epithelial cells (FT) in vivo . Recent studies have demonstrated that cancer exosomes are potential mediators of pre-metastatic niche formation, enhance VEGFR1 expression and angiogenesis in human renal cell carcinoma stem cells 35, 36 . Others have also suggested that vesicles in ascites may serve as stores of active proteinases that may aid in the metastatic process 37, 38 .…”

Breast Cancer‐Derived Exosomes Reflect the Cell‐of‐Origin Phenotype

“…The ability of these membrane‐bound vesicles to package lipids, nucleic acids, and proteins has implicated them as key mediators in cargo trafficking and intercellular communication . All exosomes contain common core proteins that reflect its biogenesis such as tetraspanins (CD9, CD63, and CD81) and TSG101 . Additionally, they contain numerous other proteins that are postulated to reflect the phenotypic and physiological state of the cell that secretes them.…”

Biological Functions and Current Advances in Isolation and Detection Strategies for Exosome Nanovesicles

“…This study also correlated CD81 with inflammation and fibrosis and suggested that exosomal CD81 may be used as a potential biomarker for the diagnosis and prognosis of hepatitis C . Several other exosomal proteins have been found to be potentially associated with the diagnosis of neurological disorders such as glioblastoma‐specific epidermal growth factor receptor vIII (EGFRvIII) in glioblastoma; EGFR, EGFRvIII, and TGF‐beta in brain tumor; exosomal amyloid peptides and phospho‐tau (Thr‐181) in Alzheimer's disease; and α‐synuclein in Parkinson's disease …”

“…Exosomes are shed by most cell types, circulate in different bodily fluids (e.g., urine, blood, and saliva) and transfer their cargo to recipient cells. These vesicles play a significant role in various pathological conditions, such as different types of cancer, neurodegenerative diseases, infectious diseases, pregnancy complications, obesity and autoimmune diseases ( Figure ). Moreover, several studies have indicated that exosomes are associated with inflammation, coagulation, angiogenesis, and apoptosis .…”