Neurotensin is a versatile modulator of in vitro human pancreatic ductal adenocarcinoma cell (PDAC) migration.
BACKGROUND
While the neurotensin (NT) roles in pancreatic cancer growth are well documented, its effects on pancreatic cancer cell migration have not been described.


METHODS
The NT-induced effects on the migration process of human pancreatic ductal adenocarcinoma cells (PDACs) were characterized by means of various assays including computer-assisted video-microscopy, fluorescence microscopy, ELISA-based, small GTPase pull-down and phosphorylation assays.


RESULTS
The NT-induced modifications on in vitro PDACs migration largely depended on the extra-cellular matrix environment and cell propensity to migrate collectively or individually. While NT significantly reduced the level of migration of collectively migrating PDACs on vitronectin, it significantly increased the level of individually migrating PDACs. These effects were mainly mediated through the sortilin/NTR3 receptor. Neurotensin both induced altered expression of alphaV and beta5 integrin subunits in PDACs cultured on vitronectin resulting in modified adhesion abilities, and caused modifications to the organization of the actin cytoskeleton through the NT-mediated activation of small Rho GTPases. While the NT effects on individually migrating PDACs were mediated at least through the EGFR/ERK signaling pathways, those on collectively migrating PDACs appeared highly dependent on the PI 3-kinase pathway.


CONCLUSIONS
This study strongly suggests the involvement of neurotensin in the modulation of human PDAC migration.
Mijatovic
Tatjana
T
Laboratory of Toxicology, Institute of Pharmacy, Free University of Brussels (ULB), Belgium.
Gailly
Philippe
P
Mathieu
Véronique
V
De Nève
Nancy
N
Yeaton
Paul
P
Kiss
Robert
R
Decaestecker
Christine
C
D000199:Actins / Q000378:metabolism; D021441:Carcinoma, Pancreatic Ductal / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D039564:Integrin alphaV / Q000378:metabolism; D039641:Integrin beta Chains / Q000378:metabolism; D008954:Models, Biological; D009496:Neurotensin / Q000494:pharmacology*; D021122:Protein Subunits / Q000378:metabolism; D018028:Receptors, Neurotensin / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D019096:Vitronectin / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D000199:Actins; D039564:Integrin alphaV; D039641:Integrin beta Chains; D021122:Protein Subunits; D018028:Receptors, Neurotensin; D019096:Vitronectin; C084344:integrin beta5; D009496:Neurotensin; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D020741:rho GTP-Binding Proteins