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Background: Invasion of pancreatic nerves by pancreatic cancer and its extension to the extrapancreaticnerve-plexus are still poorly understood events. It leads to retropancreatic tumor extension, precludes curative resection, promotes local recurrence and has a negative impact on survival. To understand the process of neural invasion, Artemin — a neurotrophic factor — and its receptors (RET-GFRα3) were studied in pancreatic cancer. Patients and Methods: Tissues from 31 patients undergoing resection for pancreatic cancer, 10 liver-metastases and 19 healthy organ donors were investigated by Westernblot-analysis, immunohistochemistry and QRT-PCR. Artemin was also determined in the pancreatic-cancer-cell-lines Colo-357, Mia-PaCa-2, BxPc-3, SU-8686, Panc-1, Capan-1, Aspc-1 and T3M4. The influence of Artemin on proliferation was analyzed via a MTT-test and its effects on the invasion was investigated by using the Biocoat-Matrigel invasion chambers. Results: Artemin-mRNA expression was increased in pancreatic cancer compared with normal pancreas. The highest and lowest levels of Artemin-mRNA in pancreatic cancer cell lines were found in T3M4 and Panc-1, respectively. Westernblot-analysis revealed increased Artemin- and its receptor-complex levels in pancreatic cancer, compared to normal pancreas. By immunohistochemistry, cancer samples exhibited strong Artemin, RET and GFRα3-immunoreactivity. Artemin did not influence cell-proliferation but increased the invasion capacity of pancreatic cancer cell-lines. Conclusion: These findings demonstrate that Artemin promotes pancreatic cancer cell invasion, but not proliferation. Its presence in metastatic cancer cells suggest that Artemin might also has an influence on the formation of metastases.