A multihormonal tumor of the pancreas producing neurotensin

Feurle, Gerhard E.; Helmstaedter, V.; Tischbirek, K.; Carraway, Robert E.; Forssmann, Wolf‐Georg; Grube, D.; Röher, H.-D.

doi:10.1007/bf01295980

Cited by 42 publications

(8 citation statements)

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“…The detection of neurotensin in a breast tumour is both new and unexpected. It is tempting to relate this to the recent finding of neurotensin in endocrine tumours of the pancreas secreting vasoactive intestinal peptide or gastrin (Blackburn et al 1981, Feurle et al 1981, Wood et al 1983, as well as in phaeochromocytomas (Tischler et al 1982). Neurotensin needs to be searched for in other breast tumours before the significance of this new observation can be properly assessed.…”

Section: Discussionmentioning

confidence: 99%

A morphological and immunocytochemical study of a distinctive variant of ductal carcinoma in‐situ of the breast

et al. 1985

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A morphological and immunocytochemid study of a distinctive variant of ductal carcinoma in sihr of the breastBecause so-called 'carcinoid' tumour of the breast has proven to be a difficult entity to define, we studied in-situ carcinoma as there were reasons to believe that this might help clarify the complex problems involved. We studied a consecutive series of 30 cases of ductal carcinoma in-sifu (DCIS) by light microscopy and silver impregnation methods and identified a relatively common endocrine variant of DCIS. This variant was studied by immunocytochemical and ultrastructural methods, using conventional DCIS as a control. Endocrine DCIS is identified by its organoid pattern, stromal 'inclusions', festooned structure and a distinctive type of polypoid invagination. It is argyrophilic and rich in neuron-specific enolase. Ultrastructurally it contains abundant dense core granules which are impregnated selectively by Grimelius' method. This tumour type frequently contains peptide hormones of the ACTH family. Three of seven cases contained cells reactive for ACI'H and corticotropin-like intermediate lobe peptide CLIP or their precursor, proopiomelanocortin. A fourth tumour contained neurotensin, recently identified in a variety of endocrine tumours. Argyrophil invasive carcinomas are a much more heterogeneous group of tumours than argyrophil DCIS and only a minority have an endocrine structure comparable to that described here.

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Section: Discussionmentioning

confidence: 99%

A morphological and immunocytochemical study of a distinctive variant of ductal carcinoma in‐situ of the breast

et al. 1985

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“…NT1 receptor autoradiography and NT1 receptor mRNA experiments revealed the NT1 receptor expression in human tumor of ovary, pancreas, and prostate, Ewing's sarcomas, meningiomas, and astrocytomas (21, 50 -52). Furthermore, it was shown that pro-NT/NN mRNA is expressed in cancer tissues and cell lines from gut, lungs, pancreas, and prostate (17)(18)(19)(20). In addition, it has been shown that the size of the tumor of human colon cancer cell or small cell lung cancer xenografted nude mice is increased by NT and inhibited by a NT1 receptor-specific antagonist, SR 48692 (53,54).…”

Section: Fig 4 Localization Of Nt1 Receptor-egfp To the Perinuclearmentioning

confidence: 99%

“…For example, the ingestion of a meal causes a prompt and prolonged rise in plasma levels of NT, lasting for at least 10 h (16). In cancer cells, mRNA of pro-NT/NN is expressed in cancer tissues and cell lines from gut (17), lungs (18), pancreas (19), and prostate (20). NT1 receptor was also found to be deregulated in several human cancers, such as ductal pancreatic adenocarcinomas (21), prostate (20), and small cell lung (22), suggesting an NT autocrine receptor activation.…”

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confidence: 99%

Receptor Trafficking via the Perinuclear Recycling Compartment Accompanied by Cell Division Is Necessary for Permanent Neurotensin Cell Sensitization and Leads to Chronic Mitogen-activated Protein Kinase Activation

Toy-Miou-Leong

Llorens-Cortes²,

Beaudet

et al. 2004

Journal of Biological Chemistry

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Most G protein-coupled receptors are internalized after interaction with their respective ligand, a process that subsequently contributes to cell desensitization, receptor endocytosis, trafficking, and finally cell resensitization. Although cellular mechanisms leading to cell desensitization have been widely studied, those responsible for cell resensitization are still poorly understood. We examined here the traffic of the high affinity neurotensin receptor (NT1 receptor) following prolonged exposure to high agonist concentration. Fluorescence and confocal microscopy of Chinese hamster ovary, human neuroblastoma (CHP 212), and murine neuroblastoma (N1E-115) cells expressing green fluorescent proteintagged NT1 receptor revealed that under prolonged treatment with saturating concentrations of neurotensin (NT) agonist, NT1 receptor and NT transiently accumulated in the perinuclear recycling compartment (PNRC). During this cellular event, cell surface receptors remained markedly depleted as detected by both confocal microscopy and 125 I-NT binding assays. In dividing cells, we observed that following prolonged NT agonist stimulation, NT1 receptors were removed from the PNRC, accumulated in dispersed vesicles inside the cytoplasm, and subsequently reappeared at the cell surface. This NT binding recovery allowed for constant cell sensitization and led to a chronic activation of mitogenactivated protein kinases p42 and p44. Under these conditions, the constant activation of NT1 receptor generates an oncogenic regulation. These observations support the potent role for neuropeptides, such as NT, in cancer progression. G protein-coupled receptors (GPCRs)1 and their agonists participate in numerous aspects of cellular and tissue regulation (1). Agonist interaction instantly leads to GPCR activation, phosphorylation, sequestration, and cell desensitization. Upon receptor endocytosis, the GPCRs may return to the cell surface directly from sorting endosomes (short cycle) (2). However, a long cycle involving the passage through the perinuclear recycling compartment (PNRC), before reaching the plasma membrane, has been suggested recently (2-4). In the present study, by examining the effect of prolonged agonist exposure on neurotensin receptor (NT1 receptor) intracellular trafficking, we determined the conditions leading to cell agonist re-sensitization, along with the physiological consequences of this recovery on intracellular signalization.Neurotensin (NT) is a brain and gastrointestinal peptide that fulfils many central and peripheral functions through its interaction with specific receptors (5, 6). Three subtypes of NT receptors have been cloned: NT1, NT2, and NT3 (7-9). NT1 and NT2 exhibit high (sub-nanomolar) and low (nanomolar) affinity for NT, respectively, and belong to the family of G proteincoupled receptors. NT3 is a single transmembrane domain receptor with 100% homology to gp95/sortilin (9). All three receptors are internalized after interaction with NT (10 -12). In the periphery, the bulk of NT is released into t...

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“…It is conceivable that the immunoreactive material is released into the general circulation where it may be implicated in the pathogenesis of paraneoplastic syndromes. Previously, NTLI has been shown to be present in endocrine pancreatic tumours (Blackburn et al, 1980;Feurle et al, 1981;Gutniak et al, 1980;Theodorsson-Norheim et al, 1983) and it also was found in human small cell lung carcinomas (Wood et al, 1981(Wood et al, , 1983. At present, the only cell lines known to produce NTLI have been derived from a rat medullary carcinoma of the thyroid and a rat phaeochromocytoma (Tischler et al, 1982;Zeytinoglu et al, 1980).…”

Section: Resultsmentioning

confidence: 99%