Figure 3.

Tumor-derived extracellular vesicles promote tumorigenesis via manipulation of the nearby sensory neurons. MicroRNAs delivered to sensory neurons regulate neuronal changes that subsequently affect tumor activity. MiR-34a from oral cavity squamous cell carcinomas inhibits neuritogenesis in nearby sensory neurons. MiR-125b inhibits BCL2 antagonist killer 1 (BAK1) translation, resulting in chemoresistance of the tumor. MiR-21 promotes sensory neuritogenesis through regulation of PTEN, PTCD4, and FASL transcripts. EphrinB1 proteins delivered to nearby neurons promote the growth of the neurons into the tumor. Damage-associated molecular pattern (DAMP) proteins, including S100A4, S100A13, BSF, and LGALS9, promote immunosuppression, which facilitates immune evasion of the tumor. MiR-324 from OCSCCs promotes neuritogenesis in nearby sensory neurons. Extracellular vesicle contents can be sampled non-invasively from a variety of body fluids, including peripheral blood, saliva, cerebrospinal fluid, and urine, among others. Extracellular vesicles promote increased crosstalk between neurons and tumors and drive a sensory to adrenergic transition in receiving neurons.