Changes in Peptidergic Innervation in Chronic Pancreatitis

Büchler, Markus W.; Weihe, Eberhard; Friess, Helmut; Malfertheiner, Peter; Bockman, EL; Müller, Sabine; Nöhr, Donatus; Hg, Beger

doi:10.1097/00006676-199203000-00009

Cited by 168 publications

(66 citation statements)

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“…NK-1R mRNA was expressed mainly in nerves and ganglia, and there was a strong relationship to the pain syndrome in these patients. These observations in chronic pancreatitis support the existence of neuroimmune interactions that seem to exist also in pancreatic cancer and might influence cancer cell behavior (Büchler et al, 1992;DiSebastiano et al, 1997;Roggo et al, 2002).…”

Section: Friess Et Alsupporting

confidence: 55%

Neurokinin-1 Receptor Expression and Its Potential Effects on Tumor Growth in Human Pancreatic Cancer

Frieß

Zhu

Liard

et al. 2003

Laboratory Investigation

108

111

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SUMMARY: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 Ͻ 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 Ͻ 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. (Lab Invest 2003, 83:731-742).

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Section: Friess Et Alsupporting

confidence: 55%

Neurokinin-1 Receptor Expression and Its Potential Effects on Tumor Growth in Human Pancreatic Cancer

Frieß

Zhu

Liard

et al. 2003

Laboratory Investigation

108

111

View full text Add to dashboard Cite

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“…Indeed, Bockman et al (1988) found ultra-structurally damaged nerves, an increase of the mean diameter of nerves and a decrease of the mean area of tissue served per nerve in chronic pancreatitis versus normal pancreas. Those nerves showed an increased expression of several neuropeptides (Buechler et al, 1992). Moreover, Shimosegawa et al (1993) discovered in chronic pancreatitis a frequent degeneration and fragmentation of nerve fibers displaying GRP-like immunoreactivity.…”

Section: Fleischmann Et Almentioning

confidence: 96%

Bombesin Receptors in Distinct Tissue Compartments of Human Pancreatic Diseases

Fleischmann

Läderach

Frieß

et al. 2000

Laboratory Investigation

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SUMMARY: Overexpression of receptors for regulatory peptides in various human diseases is reportedly of clinical interest.Among these peptides, bombesin and gastrin-releasing peptide (GRP) have been shown to play a physiological and pathophysiological role in pancreatic tissues. Our aim has been to localize bombesin receptors in the human diseased pancreas to identify potential clinical applications of bombesin analogs in this tissue. The presence of bombesin receptor subtypes has been evaluated in specimens of human pancreatic tissues with chronic pancreatitis (n ϭ 23) and ductal pancreatic carcinoma (n ϭ 29) with in vitro receptor autoradiography on tissue sections incubated with 125 ]-bombesin(6 -14) as radioligands and displaced by subtype-selective bombesin receptor agonists and antagonists. GRP receptors were identified in the pancreatic exocrine parenchyma in 17 of 20 cases with chronic pancreatitis. No measurable bombesin receptors were found in the tumor tissue of ductal pancreatic carcinomas, however, GRP receptors were detected in a subset of peritumoral small veins in 19 of 29 samples. Moreover, residual pancreatic islets in these tissues were shown to express the BB3 receptor subtype. These data demonstrate the presence of bombesin receptors in three distinct tissue compartments of the pancreas, namely GRP receptors in the exocrine parenchyma in chronic pancreatitis and in peritumoral vessels around ductal pancreatic carcinomas, and BB3 receptors in residual pancreatic islets. Such a selective expression of bombesin receptor subtypes in pancreatic tissues may not only be of pathophysiological significance but may represent the basis for potential diagnostic and therapeutic clinical applications of bombesin analogs, including GRP receptor scintigraphy to differentiate chronic pancreatitis from ductal pancreatic carcinoma.

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“…33,34 The remaining acinar cells stain brightly for pancreatic enzymes and pancreatic stone protein. 44,45 The nerves that appear enlarged express particularly calcitonin-gene related peptide and substance P. 46 Both the endothelial cells and endocrine beta and alpha cells show strong endothelin-1 expression in chronic pancreatitis. 47 …”

Section: Pathologymentioning

confidence: 99%