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Neural invasion in pancreatic cancer: a mutual tropism between neurons and cancer cells |
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| Authors: | Ceyhan Güralp O Demir Ihsan Ekin Altintas Burak Rauch Ulrich Thiel Gerald Müller Michael W Giese Nathalia A Friess Helmut Schäfer Karl-Herbert |
| Institution: | a Department of Surgery, Klinikum Rechts der Isar, Technische Universität München, Ismaningerstrasse 22, D-81675 München, Germany b Department of General Surgery, University of Heidelberg, Germany c Department of Biotechnology, University of Applied Sciences Kaiserslautern/Zweibruecken, Germany d Department of Medical Biochemistry and Molecular Biology, University of Saarland Medical Center, Homburg, Germany |
| Abstract: | Neural invasion by pancreatic cancer cells (PCC) worsens the prognosis and frequently limits curative resection. We established a novel in-vitro model in which T3M4-PCCs were co-cultured with either isolated myenteric plexus cells (MP) or dorsal root ganglia (DRG) of newborn rats within a three-dimensional extracellular matrix gel. The close vicinity of MP or DRG to T3M4-PCCs induced early morphologic changes on T3M4-PCCs at the migration front prior to the migration process with elongated and neurite-targeting PCCs, compared to round and non-grouping at the non-migrating front. T3M4-PCCs built cancer-cell clusters around the DRG or MP, a process which was accelerated by increasing number of T3M4-PCCs or neurons. These findings indicate that neuro-cancer interactions start prior to PCC migration and induce evident changes in cancer and nerve biology. These findings can be reproduced within the introduced 3D in-vitro migration assay which allows investigation in the early pathogenesis of neural PCC invasion. |
| Keywords: | Neural invasion Pancreatic cancer In-vitro migration Myenteric plexus Dorsal root ganglia NGF GDNF Artemin Persephin Neurturin |
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