Neurokinin-1 receptor expression and its potential effects on tumor growth in human pancreatic cancer

Helmut Friess, Zhaowen Zhu, Veronique Liard, Xin Shi, Shailesh V. Shrikhande, Li Wang, Klaus Lieb, Murray Korc, Carla Palma, Arthur Zimmermann, Jean Claude Reubi, Markus W. Büchler

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Abstract

The neurokinin-1 receptor (NK-1R) and its ligand substance P (SP) are involved in the pathogenesis of certain neural tumors. Because nerves are significantly altered in pancreatic cancer, evidence for alteration of this pathway in human pancreatic cancer was sought. Expression of NK-1R was analyzed by real-time quantitative RT-PCR, in situ hybridization, immunohistochemistry, and Western blot analysis in normal human pancreatic and pancreatic cancer tissue samples and in pancreatic cancer cell lines. Furthermore, the influence of SP analogs and of the NK-1R antagonist MEN 11467 on pancreatic cancer cell growth was analyzed by sulforhodamine B (SRB) assay. By real-time quantitative RT-PCR, NK-1R mRNA was increased 36.7-fold (p <0.001) in human pancreatic cancer samples compared with normal controls. Enhanced NK-1R expression levels were not related to tumor grade but were associated with advanced tumor stage and poorer prognosis. By in situ hybridization and immunohistochemistry, NK-1R mRNA and immunoreactivity were only occasionally weakly present in acinar and ductal cells in the normal pancreas. In contrast, moderate to strong NK-1R mRNA signals and immunoreactivity were present in most cancer cells. By Western blot analysis, NK-1R was increased 26-fold (p <0.01) in pancreatic cancer samples in comparison to normal controls. NK-1R mRNA was detected in five pancreatic cancer cell lines by real-time quantitative RT-PCR, with the highest levels in CAPAN-1 cells and the lowest in ASPC-1 cells. SP analogs stimulated pancreatic cancer cell growth, depending on the NK-1R expression level, and this effect could be blocked by a selective NK-1R antagonist. These findings illustrate that the NK-1R pathway is activated in human pancreatic cancer and has the potential to contribute to cancer cell growth, thus suggesting the existence of a neuro-cancer cell interaction in vivo.

Original languageEnglish (US)
Pages (from-to)731-742
Number of pages12
JournalLaboratory Investigation
Volume83
Issue number5
StatePublished - May 1 2003
Externally publishedYes

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Neurokinin-1 Receptors
Pancreatic Neoplasms
Growth
Neoplasms
Substance P
Neurokinin-1 Receptor Antagonists
Real-Time Polymerase Chain Reaction
Messenger RNA
lissamine rhodamine B
In Situ Hybridization
Western Blotting
Immunohistochemistry
Cell Line
Acinar Cells
Cell Communication
Pancreas
Ligands

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Friess, H., Zhu, Z., Liard, V., Shi, X., Shrikhande, S. V., Wang, L., ... Büchler, M. W. (2003). Neurokinin-1 receptor expression and its potential effects on tumor growth in human pancreatic cancer. Laboratory Investigation, 83(5), 731-742.

Neurokinin-1 receptor expression and its potential effects on tumor growth in human pancreatic cancer. / Friess, Helmut; Zhu, Zhaowen; Liard, Veronique; Shi, Xin; Shrikhande, Shailesh V.; Wang, Li; Lieb, Klaus; Korc, Murray; Palma, Carla; Zimmermann, Arthur; Reubi, Jean Claude; Büchler, Markus W.

In: Laboratory Investigation, Vol. 83, No. 5, 01.05.2003, p. 731-742.

Research output: Contribution to journalArticle

Friess, H, Zhu, Z, Liard, V, Shi, X, Shrikhande, SV, Wang, L, Lieb, K, Korc, M, Palma, C, Zimmermann, A, Reubi, JC & Büchler, MW 2003, 'Neurokinin-1 receptor expression and its potential effects on tumor growth in human pancreatic cancer', Laboratory Investigation, vol. 83, no. 5, pp. 731-742.
Friess H, Zhu Z, Liard V, Shi X, Shrikhande SV, Wang L et al. Neurokinin-1 receptor expression and its potential effects on tumor growth in human pancreatic cancer. Laboratory Investigation. 2003 May 1;83(5):731-742.
Friess, Helmut ; Zhu, Zhaowen ; Liard, Veronique ; Shi, Xin ; Shrikhande, Shailesh V. ; Wang, Li ; Lieb, Klaus ; Korc, Murray ; Palma, Carla ; Zimmermann, Arthur ; Reubi, Jean Claude ; Büchler, Markus W. / Neurokinin-1 receptor expression and its potential effects on tumor growth in human pancreatic cancer. In: Laboratory Investigation. 2003 ; Vol. 83, No. 5. pp. 731-742.
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abstract = "The neurokinin-1 receptor (NK-1R) and its ligand substance P (SP) are involved in the pathogenesis of certain neural tumors. Because nerves are significantly altered in pancreatic cancer, evidence for alteration of this pathway in human pancreatic cancer was sought. Expression of NK-1R was analyzed by real-time quantitative RT-PCR, in situ hybridization, immunohistochemistry, and Western blot analysis in normal human pancreatic and pancreatic cancer tissue samples and in pancreatic cancer cell lines. Furthermore, the influence of SP analogs and of the NK-1R antagonist MEN 11467 on pancreatic cancer cell growth was analyzed by sulforhodamine B (SRB) assay. By real-time quantitative RT-PCR, NK-1R mRNA was increased 36.7-fold (p <0.001) in human pancreatic cancer samples compared with normal controls. Enhanced NK-1R expression levels were not related to tumor grade but were associated with advanced tumor stage and poorer prognosis. By in situ hybridization and immunohistochemistry, NK-1R mRNA and immunoreactivity were only occasionally weakly present in acinar and ductal cells in the normal pancreas. In contrast, moderate to strong NK-1R mRNA signals and immunoreactivity were present in most cancer cells. By Western blot analysis, NK-1R was increased 26-fold (p <0.01) in pancreatic cancer samples in comparison to normal controls. NK-1R mRNA was detected in five pancreatic cancer cell lines by real-time quantitative RT-PCR, with the highest levels in CAPAN-1 cells and the lowest in ASPC-1 cells. SP analogs stimulated pancreatic cancer cell growth, depending on the NK-1R expression level, and this effect could be blocked by a selective NK-1R antagonist. These findings illustrate that the NK-1R pathway is activated in human pancreatic cancer and has the potential to contribute to cancer cell growth, thus suggesting the existence of a neuro-cancer cell interaction in vivo.",
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AU - Lieb, Klaus

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