The Parkinson's disease-associated protein α-synuclein inhibits hepatoma by exosome delivery.

ABSTRACT

Numerous epidemiological studies suggest a link between Parkinson's disease (PD) and cancer. However, their relevant pathogenesis is not clear. In the present study, we investigated the potential role of exosome-delivered α-synuclein (α-syn) in the regulation between PD and liver cancer. We cultured hepatocellular carcinoma (HCC) cells with exosomes derived from conditioned medium of the PD cellular model, and injected exosomes enriched with α-syn into the striatum of a liver cancer rat model. We found that α-syn-contained exosomes from the rotenone-induced cellular model of PD suppressed the growth, migration, and invasion of HCC cells. Integrin αVß5 in exosomes from the rotenone-induced PD model was higher than that in the control, resulting in more α-syn-contained exosomes being taken up by HCC cells. Consistently, in vivo experiments with rat models also confirmed exosome-delivered α-syn inhibited liver cancer. These findings illustrate the important role of PD-associated protein α-syn inhibiting hepatoma by exosome delivery, suggesting a new mechanism underlying the link between these two diseases and therapeutics of liver cancer.