Exosomes in the Tumor Microenvironment: From Biology to Clinical Applications

Abstract

Cancer is one of the most important health problems and the second leading cause of death worldwide. Despite the advances in oncology, cancer heterogeneity remains challenging to therapeutics. This is because the exosome-mediated crosstalk between cancer and non-cancer cells within the tumor microenvironment (TME) contributes to the acquisition of all hallmarks of cancer and leads to the formation of cancer stem cells (CSCs), which exhibit resistance to a range of anticancer drugs. Thus, this review aims to summarize the role of TME-derived exosomes in cancer biology and explore the clinical potential of mesenchymal stem-cell-derived exosomes as a cancer treatment, discussing future prospects of cell-free therapy for cancer treatment and challenges to be overcome.

Lipid Metabolism in Cancer: The Role of Acylglycerolphosphate Acyltransferases (AGPATs)

“…In addition, PA was found to be enriched in exosome membranes of PC-3 prostate cancer cells [ 108 ]. Cancer cells can use these secretory vesicles and their cargo to manipulate the tumor microenvironment and establish distal pre-metastatic niches [ 109 , 110 ].…”

Advances in Cellular and Cell-Free Therapy Medicinal Products for Huntington Disease Treatment

“…This is because, due to the repertoire of bioactive molecules carried by these vesicles (coding and non-coding RNA, proteins, lipids, and metabolites), the exosomes play an important role in cell-to-cell communication and intercellular signaling, regulating both physiological and pathophysiological processes. Moreover, in the function of their nanosize (30-200 nm), exosomes easily cross the blood-brain barrier [1,25].…”

“…Along with the maturation of early endosomes to late endosomes, some proteins are directly integrated into the invaginating membrane. However, this process depends on the endosomal sorting complexes required for transport (ESCRTs), which are comprised of four proteins (ESCRT-0, ESCRT-I, ESCRT-II, and ESCRT-III) that work cooperatively to facilitate the MVB formation, vesicle budding, and protein cargo sorting [1,25]. The exosomes biogenesis also occurs through an ESCRT-independent pathway mediated by tetraspanins and ceramide-enriched lipid rafts.…”

“…The exosomes biogenesis also occurs through an ESCRT-independent pathway mediated by tetraspanins and ceramide-enriched lipid rafts. Tetraspanins are recruited at early steps to endosome membranes before ILV formation, and at least CD9, CD63, CD81, and CD82 are found in endosome and exosome membranes [1,25].…”

“…Since the discovery of HTT gene mutation (in 1993), it has been recognized that larger CAG expansions are associated with early-onset in HD, especially for AOHD. Generally, unaffected individuals have less than 35 CAG repeats (common rage in humans: [17][18][19][20][21][22][23][24][25], while affected individuals have 36-250 CAG repeats. The CAG repeat range of 36-39 might be found in affected individuals and asymptomatic individuals (reduced penetrance alleles), whereas individuals with over 40 CAG repeats always develop the disease (fully penetrance alleles) [4].…”