Gut peptide receptor expression in human pancreatic cancers. Ann Surg 2000 Jun;231(6):838-48
Date
05/19/2000Pubmed ID
10816627Pubmed Central ID
PMC1421073DOI
10.1097/00000658-200006000-00008Scopus ID
2-s2.0-0034082312 (requires institutional sign-in at Scopus site) 69 CitationsAbstract
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 micromol/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.
Author List
Ehlers RA, Kim Sh, Zhang Y, Ethridge RT, Murrilo C, Hellmich MR, Evans DB, Townsend CM Jr, Mark Evers BAuthor
Douglas B. Evans MD Chair, Professor in the Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdenocarcinomaHumans
Pancreatic Neoplasms
Receptors, Bombesin
Receptors, Neurokinin-1
Receptors, Neuropeptide
Receptors, Vasoactive Intestinal Peptide
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
Tumor Cells, Cultured
