Roles of extracellular vesicles in the bladder cancer field cancerization effect

The existence of a pre-malignant field that is predisposed to tumor formation is called the cancer field effect. First described in the 1950s, its causes remain largely unknown. Recently, the discovery of extracellular vesicles and their functions in cell-cell communication has opened a new avenue of understanding cancer biology. In this project, we study the field effect in bladder cancer and show that bladder cancer extracellular vesicles transfer information in a paracrine/endocrine manner to induce reprogramming of recipient normal cells in the “field”, consequently inducing malignant transformation. Importantly, we identify signal pathways associated with extracellular vesicle-induced tumorigenesis which can be therapeutically targeted. In summary, this study investigates a potentially fundamental contributor to the bladder cancer field effect, provides desperately needed markers of disease recurrence, progression, and response to therapy, and the identified pathways will provide novel therapeutic targets to inhibit development of future tumors in the field.

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