The Role of Exosomes in the Progression and Therapeutic Resistance of Hematological Malignancies

Abstract

Exosomes are membrane limited structures which derive from cell membranes and cytoplasm. When released into extracellular space, they circulate through the extracellular fluid, including the peripheral blood and tissue fluid. Exosomes surface molecules mediate their targeting to specific recipient cells and deliver their contents to recipient cells by receptor-ligand interaction and/or phagocytosis and/or endocytosis or direct fusion with cell membrane. Exosomes contain many functional molecules, including nucleic acids (DNAs, mRNAs, non-coding RNAs), proteins (transcription factors, enzymes), and lipids which have biological activity. By passing these cargos, exosomes can transfer information between cells. In this way, exosomes are extensively involved in physiological and pathological processes, such as angiogenesis, matrix reprogramming, coagulation, tumor progression. In recent years, researcher have found that exosomes from malignant tumors can mediate information exchange between tumor cells or between tumor cells and non-tumor cells, thereby promoting tumor survival, progression, and resistance to therapy. In this review, we discuss the pro-tumor and anti-therapeutic effects of exosomes in hematological malignancies, hoping to contribute to the early conquest of hematological malignancy.

Drug Resistance in Cancers: A Free Pass for Bullying

“…Complement has been shown to enhance the antitumor activity of molecular-targeted inhibitors by encouraging the formation of membrane attack complexes (MACs), which are strong drivers of cell lysis. TDEs contain extensive kinase casein kinase 2 (CK2), which phosphorylates complement C9 and protects B lymphoma cells from complement-dependent cytotoxicity (CDC), thereby inducing rituximab resistance [ 139 ]. Mortalin/GRP75 from oligodendroglioma-derived exosomes promotes the abscission of membrane vesicles loaded with MAC and protects tumor cells from temozolomide-mediated cytotoxicity [ 140 ].…”

Crosstalk among long non-coding RNA, tumor-associated macrophages and small extracellular vesicles in tumorigenesis and dissemination

“…sEV can alter the physiological state of recipient cells via different mechanisms. For example, sEV can directly attach to recipient cells through their surface molecules via receptor-ligand interactions ( 24 , 25 ) or fuse with the target cell membrane to transport their contents into the cytosol ( 8 , 26 ). sEV are derived from tumor cells and other cells of the TME, including fibroblasts, endothelial and immune cells, and have different signatures based on their origin ( 27 ).…”