Gut peptide receptor expression in human pancreatic cancers

Richard A. Ehlers, Sung Hoon Kim, Yujin Zhang, Richard T. Ethridge, Carlos Murrilo, Mark Hellmich, Douglas B. Evans, Courtney Townsend, B. Mark Evers

Research output: Contribution to journalArticle

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Abstract

Objective: To determine the prevalence of gastrointestinal (GI) peptide receptor expression in pancreatic cancers, and to further assess signaling mechanisms regulating neurotensin (NT)-mediated pancreatic cancer growth. Summary Background Data: Pancreatic cancer remains one of the leading causes of GI cancer death; novel strategies for the early detection and treatment of these cancers is required. Previously, the authors have shown that NT, an important GI hormone, stimulates the proliferation of an NT receptor (NTR)- positive pancreatic cancer. Methods: A total of 26 human pancreatic adenocarcinomas, obtained after resection, and 5 pancreatic cancer xenografts were analyzed for expression of NTR, vasoactive intestinal peptide receptor (VIPR), substance P receptor (SPR), and gastrin-releasing peptide receptor (GRPR). In addition, NTR expression, [Ca2+](i) mobilization, and growth in response to NT was determined in L3.6, a metastatic pancreatic cancer cell line. Results: Neurotensin receptor was expressed in 88% of the surgical specimens examined and all five of the pancreatic cancer xenografts. In contrast, VIPR, SPR, and GRPR expression was detected in 31%, 27%, and 8% of pancreatic cancers examined, respectively. Expression of NTR, functionally coupled to the Ca2+ signaling pathway, was identified in L3.6 cells; treatment with NT (10 μmol/L) stimulated proliferation of these cells. Conclusions: The authors demonstrated NTR expression in most of the pancreatic adenocarcinomas examined. In contrast, VIPR, SPR, and GRPR expression was detected in fewer of the pancreatic cancers. The expression of NTR and other peptide receptors suggests the potential role of endocrine manipulation in the treatment of these cancers. Further, the presence of GI receptors may provide for targeted chemotherapy or radiation therapy or in vivo scintigraphy for early detection.

Original languageEnglish (US)
Pages (from-to)838-848
Number of pages11
JournalAnnals of Surgery
Volume231
Issue number6
DOIs
StatePublished - Jun 2000

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Peptide Receptors
Pancreatic Neoplasms
Neurotensin
Vasoactive Intestinal Peptide Receptors
Bombesin Receptors
Neurokinin-1 Receptors
Neurotensin Receptors
Heterografts
Gastrointestinal Hormone Receptors
Adenocarcinoma
Gastrointestinal Hormones
Gastrointestinal Neoplasms
Growth
Early Detection of Cancer
Radionuclide Imaging
Radiotherapy
Therapeutics
Cell Proliferation
Drug Therapy
Cell Line

ASJC Scopus subject areas

  • Surgery

Cite this

Ehlers, R. A., Kim, S. H., Zhang, Y., Ethridge, R. T., Murrilo, C., Hellmich, M., ... Evers, B. M. (2000). Gut peptide receptor expression in human pancreatic cancers. Annals of Surgery, 231(6), 838-848. https://doi.org/10.1097/00000658-200006000-00008

Gut peptide receptor expression in human pancreatic cancers. / Ehlers, Richard A.; Kim, Sung Hoon; Zhang, Yujin; Ethridge, Richard T.; Murrilo, Carlos; Hellmich, Mark; Evans, Douglas B.; Townsend, Courtney; Evers, B. Mark.

In: Annals of Surgery, Vol. 231, No. 6, 06.2000, p. 838-848.

Research output: Contribution to journalArticle

Ehlers, RA, Kim, SH, Zhang, Y, Ethridge, RT, Murrilo, C, Hellmich, M, Evans, DB, Townsend, C & Evers, BM 2000, 'Gut peptide receptor expression in human pancreatic cancers', Annals of Surgery, vol. 231, no. 6, pp. 838-848. https://doi.org/10.1097/00000658-200006000-00008
Ehlers, Richard A. ; Kim, Sung Hoon ; Zhang, Yujin ; Ethridge, Richard T. ; Murrilo, Carlos ; Hellmich, Mark ; Evans, Douglas B. ; Townsend, Courtney ; Evers, B. Mark. / Gut peptide receptor expression in human pancreatic cancers. In: Annals of Surgery. 2000 ; Vol. 231, No. 6. pp. 838-848.
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abstract = "Objective: To determine the prevalence of gastrointestinal (GI) peptide receptor expression in pancreatic cancers, and to further assess signaling mechanisms regulating neurotensin (NT)-mediated pancreatic cancer growth. Summary Background Data: Pancreatic cancer remains one of the leading causes of GI cancer death; novel strategies for the early detection and treatment of these cancers is required. Previously, the authors have shown that NT, an important GI hormone, stimulates the proliferation of an NT receptor (NTR)- positive pancreatic cancer. Methods: A total of 26 human pancreatic adenocarcinomas, obtained after resection, and 5 pancreatic cancer xenografts were analyzed for expression of NTR, vasoactive intestinal peptide receptor (VIPR), substance P receptor (SPR), and gastrin-releasing peptide receptor (GRPR). In addition, NTR expression, [Ca2+](i) mobilization, and growth in response to NT was determined in L3.6, a metastatic pancreatic cancer cell line. Results: Neurotensin receptor was expressed in 88{\%} of the surgical specimens examined and all five of the pancreatic cancer xenografts. In contrast, VIPR, SPR, and GRPR expression was detected in 31{\%}, 27{\%}, and 8{\%} of pancreatic cancers examined, respectively. Expression of NTR, functionally coupled to the Ca2+ signaling pathway, was identified in L3.6 cells; treatment with NT (10 μmol/L) stimulated proliferation of these cells. Conclusions: The authors demonstrated NTR expression in most of the pancreatic adenocarcinomas examined. In contrast, VIPR, SPR, and GRPR expression was detected in fewer of the pancreatic cancers. The expression of NTR and other peptide receptors suggests the potential role of endocrine manipulation in the treatment of these cancers. Further, the presence of GI receptors may provide for targeted chemotherapy or radiation therapy or in vivo scintigraphy for early detection.",
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