By Hala Gali-Muhtasib

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However, they show a great potential for future developments in the diagnostic and prognostic applications. 5. Targeting interactions of membrane vesicles with neighboring tumor microenvironment Tumor cells release large quantities of exosomes containing procoagulant, growth regulatory, and oncogenic cargo, which can be transferred throughout the cancer cell population and to transformed stromal cells, endothelial cells and possibly to the inflammatory infiltrates. These events likely impact tumor invasion, angiogenesis, metastasis, drug resistance, and cancer stem cells.

Ubiquitin marks cargo proteins for endosomal sorting. Monoubiquitination appears to mark cargo proteins for protein sorting within the MVBs. In yeast, recruitment of ubiquitinated cargo proteins depends on a class of proteins known as class E Vps (Vacuolar Protein Sorting) proteins that have been highly conserved from yeast to mammals—at least one mammalian homolog has been identified for each yeast class member (Babst, 2005). In the yeast model, Vps 27, is thought to complex on the endosomal membrane’s outer leaflet with clathrin and ubiquitin-binding proteins, such as Golgiassociated, γ-adaptin homologs, Arf-binding (GGA) proteins, to form an endosomal clathrin coat that recruits monoubiquitinated cargo to the inner leaflet of the endosomal membrane.

Release of FasL via exosomes allows the tumor to kill FasRexpressing immune cells at distant sites, as well as in the tumor microenvironment, further preventing tumor clearance. , 2005a). The mechanism behind this is not fully understood, but may be due to favored interactions between exosomes and cytotoxic T cells due to other exosomal surface molecules (Figure 7). 4 Tumor exosomes induce suppressive immune cell phenotypes Immune suppression within the tumor microenvironment prevents cytotoxic attack and promotes tumor progression.

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Advances in Cancer Therapy by Hala Gali-Muhtasib
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