Role of Exosomes in Cancer

Exosomes, 30†100nm membrane vesicles, released by most cell types including tumorcells. They contain cytosolic and membrane proteins derived from the parental cells. Tumorderivedexosomes (TDEs) contain tumor antigens, immunosuppressive proteins andfunctional RNAs. They are recognized as mediators of cell-to-cell communication. TDEs: 1)interact with target cells for direct stimulation of them via surface-expressed growth factors orbioactive lipids, transfer of membrane receptors, or delivery of proteins to target cells. 2)Induce antitumor responses when the parental tumor cells were genetically modified toexpress proinflammatory-cytokines. 3) Express death ligand and trigger the apoptotic deathof activated effector T cells, thus directly suppress these cells. 4) Negatively regulate theeffector arm of the immune system, in particular T and NK cells. 5) Target myeloid cells tomodulate their differentiation and function. 6) Support the function of regulatory T cells. 7) arecapable of altering APC function and can promote tolerance to tumor-specific antigens. 8)Establish a premetastatic niche and facilitate tumor invasion and metastasis. 9) TransferNotch ligand Delta-like into the cell membrane of host endothelial cells, resulting in theinhibition of Notch signaling and the switch of endothelial cell phenotype toward tip cells. 10)Transport of RNAs and Proteins from tumor to neighboring cells and transportapoptosisinhibitory proteins induced under stress conditions for Tumor Survival and Growth.11) Participate in drug resistance through several mechanisms. Exosomes isolated frombody fluids containing tumor-specific protein and microRNA profiles can be cancer diagnosticmarkers. However TDEs with a chimeric membrane surface tag could not be detected inplasma. Therefore, different types of tumor growth patterns affect the accumulation of TDEs inperipheral circulation. In other hand, the promising results obtained in animal models led tophase I clinical trials using TDEs as cancer vaccines.

کلیدواژه ها:

Cancer ، Exosomes ، Diagnosis ، Treatment ، Functions