Abstract
Neuromedin U is predominantly expressed in the CNS and gastrointestinal tract. Microarray analysis of human tissue specimens of normal pancreas, chronic pancreatitis and pancreatic cancer revealed a cancer-specific overexpression of NmU. Therefore, to investigate the potential of NmU as a diagnostic marker in pancreatic cancer and a putative role of NmU in PDAC pathogenesis were the subject of current investigation.
Expression of NmU and its receptors NmUR1 & 2 were characterized in pancreatic cancer cell lines, human pancreatic specimens of normal pancreas, chronic pancreatitis and PDAC by quantitative RT-PCR, immunohistochemistry and Western Blot analysis. An ELISA was used to compare pre- and postoperative NmU serum levels in 10 pancreatic cancer patients and 5 chronic pancreatitis patients. In vitro, effects of NmU on cell proliferation and migration were tested using pancreatic cancer cell lines.
A significant overexpression of NmU and NmUR2 mRNA in cancer and metastatic tissues was found by QT-PCR. According to IHC, protein expression was localized predominantly in cancer ducts but also hypertrophic nerves and tubular complexes in primary tumors and in cancer cells of metastasic lesions. Serum levels of NmU were not significantly higher in cancer patients compared to patients suffering from chronic pancreatitis, however individual NmU-serum levels dropped considerably after tumor resection indicating NmU as a possible serum marker for tumor recurrence. No significant effect of exogenous NmU-25 on cell proliferation could be detected. However, NmU treatment promoted rHGF-induced scattering of tumor cells, presumably through an up-regulation of c-met oncogene expression.
In conclusion we show that NmU and its receptor NmUR2 are over-expressed in pancreatic cancer on mRNA and on protein level. Besides its role as a clinical marker, we suggest an involvement of NmU in the HGF-Met paracrine loop regulating cell migration and thus invasive tumor growth and dissemination of cancer cells in PDAC.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Literaturangaben
Minamino N, Kangawa K, and Matsuo H (1985) Neuromedin U-8 and U-25: novel uterus stimulating and hypertensive peptides identified in porcine spinal cord. Biochem Biophys Res Commun 130:1078–1085
Brighton PJ, Szekeres PG, and Willars GB (2004) Neuromedin U and its receptors: structure, function, and physiological roles. Pharmacol Rev 56:231–248
Ma PC, Maulik G, Christensen J, and Salgia R (2003) c-Met: structure, functions and potential for therapeutic inhibition. Cancer Metastasis Rev 22:309–325
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2005 Springer Medizin Verlag Heidelberg
About this paper
Cite this paper
Ketterer, K., Frank, D., Giese, N., Büchler, M.W., Friess, H. (2005). Spezifische Überexpression von Neuromedin U erhöht die Invasivität durch c-met Regulation beim Pankreaskarzinom. In: Rothmund, M., Jauch, KW., Bauer, H. (eds) Chirurgisches Forum 2005. Deutsche Gesellschaft für Chirurgie, vol 34. Springer, Berlin, Heidelberg. https://doi.org/10.1007/3-540-26560-0_22
Download citation
DOI: https://doi.org/10.1007/3-540-26560-0_22
Publisher Name: Springer, Berlin, Heidelberg
Print ISBN: 978-3-540-24888-0
Online ISBN: 978-3-540-26560-3
eBook Packages: Medicine (German Language)