Neural invasion in pancreatic cancer: a mutual tropism between neurons and cancer cells.
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.
Ceyhan
Güralp O
GO
Department of Surgery, Klinikum Rechts der Isar, Technische Universität München, Ismaningerstrasse 22, D-81675 München, Germany. ceyhan@chir.med.tu-muenchen.de
Demir
Ihsan Ekin
IE
Altintas
Burak
B
Rauch
Ulrich
U
Thiel
Gerald
G
Müller
Michael W
MW
Giese
Nathalia A
NA
Friess
Helmut
H
Schäfer
Karl-Herbert
KH
D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D018920:Coculture Techniques; D005727:Ganglia, Spinal / Q000473:pathology; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006801:Humans; D009197:Myenteric Plexus / Q000473:pathology; D009361:Neoplasm Invasiveness; D020932:Nerve Growth Factor / Q000494:pharmacology; D016501:Neurites / Q000187:drug effects / Q000473:pathology*; D009474:Neurons / Q000187:drug effects / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000473:pathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018523:Tropism
D051100:Glial Cell Line-Derived Neurotrophic Factor; D020932:Nerve Growth Factor