Neuromedin U is overexpressed in pancreatic cancer and increases invasiveness via the hepatocyte growth factor c-Met pathway.
Neuromedin U (NmU) is a bioactive peptide, ubiquitously expressed in the gastrointestinal tract. Here, we analyzed the role of NmU in pancreatic ductal adenocarcinoma (PDAC) pathogenesis. NmU and NmU receptor-2 mRNA were significantly overexpressed in PDAC and in metastatic tissues. NmU and NmU receptor-2 were localized predominantly in cancer cells. NmU serum levels decreased after tumor resection. Although NmU exerted no effects on cancer cell proliferation, it induced c-Met and a trend towards increased invasiveness as well as an increased hepatocyte growth factor (HGF)-mediated scattering. Thus, NmU may be involved in the HGF-c-Met paracrine loop regulating cell migration, invasiveness and dissemination of PDAC.
Ketterer
Knut
K
Department of Surgery, Technische Universität München, Ismaningerstrasse 22, Munich, Germany.
Kong
Bo
B
Frank
Dietwalt
D
Giese
Nathalia A
NA
Bauer
Andrea
A
Hoheisel
Jörg
J
Korc
Murray
M
Kleeff
Jörg
J
Michalski
Christoph W
CW
Friess
Helmut
H
D000230:Adenocarcinoma / Q000473:pathology*; D021441:Carcinoma, Pancreatic Ductal / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017228:Hepatocyte Growth Factor / Q000502:physiology*; D006801:Humans; D009361:Neoplasm Invasiveness; D009479:Neuropeptides / Q000097:blood / Q000235:genetics / Q000502:physiology*; D010190:Pancreatic Neoplasms / Q000097:blood / Q000473:pathology* / Q000601:surgery; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics / Q000502:physiology*; D017981:Receptors, Neurotransmitter / Q000235:genetics / Q000502:physiology
D009479:Neuropeptides; D017981:Receptors, Neurotransmitter; C082444:neuromedin U receptor; C056900:neuromedin U; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met