The uncovering and characterization of a CCKoma syndrome in enteropancreatic neuroendocrine tumor patients

Rehfeld, Jens F.; Federspiel, Birgitte; Agersnap, Mikkel; Knigge, Ulrich; Bardram, Linda

doi:10.1080/00365521.2016.1183706

Cited by 21 publications

(10 citation statements)

References 37 publications

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“…Cholecystokinin is expressed at highly variable amounts in different neuroendocrine tumors, especially corticotrophic pituitary tumors (44), medullary thyroid carcinomas (17), phaeochromocytomas (98), and pancreatic islet cell tumors of which some may cause a specific CCKoma syndrome (114–117). CCK is also expressed in Ewing’s Sarcomas, where proCCK measurements may be used to monitor the treatment (118).…”

Section: Novel Sites Of Expressionmentioning

confidence: 99%

Cholecystokinin—From Local Gut Hormone to Ubiquitous Messenger

2017

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Cholecystokinin (CCK) was discovered in 1928 in jejunal extracts as a gallbladder contraction factor. It was later shown to be member of a peptide family, which are all ligands for the CCK1 and CCK2 receptors. CCK peptides are known to be synthetized in small intestinal endocrine I-cells and cerebral neurons. But in addition, CCK is expressed in several endocrine glands (pituitary cells, thyroid C-cells, pancreatic islets, the adrenals, and the testes); in peripheral nerves; in cortical and medullary kidney cells; in cardial myocytes; and in cells of the immune system. CCK peptides stimulate pancreatic enzyme secretion and growth, gallbladder contraction, and gut motility, satiety and inhibit acid secretion from the stomach. Moreover, they are major neurotransmitters in the brain and the periphery. CCK peptides also stimulate calcitonin, insulin, and glucagon secretion, and they may act as natriuretic peptides in the kidneys. CCK peptides are derived from proCCK with a C-terminal bioactive YMGWMDFamide sequence, in which the Y-residue is partly O-sulfated. The plasma forms are CCK-58, -33, -22, and -8, whereas the small CCK-8 and -5 are potent neurotransmitters. Over the last decades, CCK expression has also been encountered in tumors (neuroendocrine tumors, cerebral astrocytomas, gliomas, acoustic neuromas, and specific pediatric tumors). Recently, a metastastic islet cell tumor was found to cause a specific CCKoma syndrome, suggesting that circulating CCK may be a useful tumor marker.

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Section: Novel Sites Of Expressionmentioning

confidence: 99%

Cholecystokinin—From Local Gut Hormone to Ubiquitous Messenger

2017

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“…Receptoractivated permanent gallbladder contraction, however, is inexpedient and may result in cholelithiasis and other gallbladder problems. 82 Therefore, sulphated CCK-like peptides should probably not be used for therapy of human diabetes. The CCK analogues under study were recently reviewed.…”

Section: Gastrin and Cck Analogues For Diabetes Therapymentioning

confidence: 99%

“…65-77 Sixth, there is the well-known occurrence of gastrin- and CCK-producing neuroendocrine tumours from pancreatic islets. 78-83 And, finally, there is the incretin effect of gastrin and CCK peptides as described below. The biological linkages of CCK and gastrin to islet cells are summarized in Table 3.…”

Section: The Biological Linkage Of Gastrin and Cck To Pancreatic Isletsmentioning

confidence: 99%

Premises for Cholecystokinin and Gastrin Peptides in Diabetes Therapy

Rehfeld

2019

Clin Med Insights Endocrinol Diabetes

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Gastrin and cholecystokinin (CCK) are classical gastrointestinal peptide hormones. Their biogenesis, structures, and intestinal secretory patterns are well-known with the striking feature that their receptor-bound 'active sites' are highly homologous and that this structure is conserved for more than 500 million years during evolution. Consequently, gastrin and CCK are agonists for the same receptor (the CCK 2 receptor). But in addition, tyrosyl O-sulphated CCK are also bound to the specific CCK 1 receptor. The receptors are widely expressed in the body, including pancreatic islet-cell membranes. Moreover, CCK and gastrin peptides are at various developmental stages and diseases expressed in pancreatic islets; also in human islets. Accordingly, bioactive gastrin and CCK peptides stimulate islet-cell growth as well as insulin and glucagon secretion. In view of their insulinotropic effects, gastrin and CCK peptides have come into focus as drug targets, either alone or in combination with other insulinotropic gut hormones or growth factors. So far, modified CCK and gastrin peptides are being examined as potential drugs for therapy of type 1 as well as type 2 diabetes mellitus.

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“…The cholecystokinin gene is expressed at highly variable amounts in different neuroendocrine tumors, especially corticotrophic pituitary tumors (130), medullary thyroid carcinomas (116), phaeochromocytomas (118), and pancreatic islet cell tumors of which some may cause a specific clinical CCKoma syndrome (131)(132)(133)(134). The CCK gene is also expressed in Ewing's sarcomas, where proCCK is apparently is poorly processed.…”

Section: Cck In Tumor Cellsmentioning

confidence: 99%

Cholecystokinin and the hormone concept

Rehfeld

2021

Endocrine Connections

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The birth certificate for endocrinology was Bayliss’ and Starling’s demonstration in 1902 that regulation of bodily functions is not only neuronal, but due also to blood-borne messengers. Starling named these messengers hormones. Since then, transport via blood has defined hormones. This definition, however, may be too narrow. Thus, today we know that several peptide hormones not only are produced and released to blood from endocrine cells. They are released also from neurons, myocytes, immune cells, endothelial cells, spermatogenic cells, fat cells, etc. And they are often secreted in cell-specific molecular forms with more or less different spectra of activity. The present review depicts this development with the story about cholecystokinin, which was discovered in 1928 as a hormone and still in 1976 was conceived as a single blood-borne peptide. Todays’ multifaceted picture of cholecystokinin suggests that time may be ripe for expansion of the hormone concept to all messenger molecules, which activate their target cells – irrespective of their road to the target (endocrine, neurocrine, neuronal, paracrine, autocrine, etc.) and irrespective of their kind of activity as classical hormone; growth factor; neurotransmitter; adipokine; cytokine; myokine; or fertility factor.

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The uncovering and characterization of a CCKoma syndrome in enteropancreatic neuroendocrine tumor patients

Abstract: A CCKoma syndrome with severe hypersecretion of CCK exists in man. The duodenal ulcer disease and diarrhea with permanently low gastrin in plasma suggest that CCKomas may mimic gastrinoma-like symptoms, because CCK peptides are full agonists of the gastrin/CCK-B receptor.

Cited by 21 publications

References 37 publications

Cholecystokinin—From Local Gut Hormone to Ubiquitous Messenger

Cholecystokinin—From Local Gut Hormone to Ubiquitous Messenger

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Cholecystokinin and the hormone concept

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