Neurotrophic Factor Artemin Promotes Invasiveness and Neurotrophic Function of Pancreatic Adenocarcinoma In Vivo and In Vitro

Abstract

ObjectivesThe aim of this study was to investigate the effect of the neurotrophic factor Artemin on neuroplasticity and perineural invasion of pancreatic adenocarcinoma.MethodsArtemin expressions were detected in human pancreatic adenocarcinoma tissues by Western blot and immunohistochemistry. Artemin overexpression and RNA interference in the pancreatic cancer cell lines were performed to evaluate the effects of Artemin on cell proliferation, invasion, and neurotrophic activity in vitro and in nude orthotopic transplantation tumor models.ResultsArtemin expression in pancreatic cancer tissues was related to the incidence of lymphatic metastasis and perineural invasion as well as the mean density and total area of nerve fibers. Overexpression of Artemin in pancreatic cancer cell lines improved colony formation, cell migration, matrigel invasion, and neurotrophic activity in vitro. This overexpression also increased the volume of nude orthotopic transplantation tumors; promoted cancer cell invasion of the peripheral organs, nerves, vessels, and lymph nodes; and stimulated the proliferation of peritumoral nerve fibers. Artemin depletion by RNA interference had an inhibitory effect mentioned previously.ConclusionsArtemin could promote invasiveness and neurotrophic function of pancreatic adenocarcinoma in vivo and in vitro. Therefore, Artemin could be used as a new therapeutic target of pancreatic carcinoma.