Cholecystokinin Expression in Tumors: Biogenetic and Diagnostic Implications

2017

Front. Endocrinol.

181

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.

Section: Novel Sites Of Expressionmentioning

confidence: 99%

Cholecystokinin—From Local Gut Hormone to Ubiquitous Messenger

2017

Front. Endocrinol.

181

“…Diagnostically, measurements of CCK in tumor extracts and immunocytochemistry have been used to demonstrate CCK expression in different benign and malignant tumours 131,132,154–162 . Generally, the tumor cell level and secretion have been too low to significantly increase the plasma concentrations of CCK.…”

Section: Cholecystokinin: Extraintestinal Expression and Clinical Sig...mentioning

confidence: 99%

History of key regulatory peptide systems and perspectives for future research

Chen

Watts

et al. 2023

J Neuroendocrinology

Throughout the 20th Century, regulatory peptide discovery advanced from the identification of gut hormones to the extraction and characterization of hypothalamic hypophysiotropic factors, and to the isolation and cloning of multiple brain neuropeptides. These discoveries were followed by the discovery of G‐protein‐coupled and other membrane receptors for these peptides. Subsequently, the systems physiology associated with some of these multiple regulatory peptides and receptors has been comprehensively elucidated and has led to improved therapeutics and diagnostics and their approval by the US Food and Drug Administration. In light of this wealth of information and further potential, it is truly a time of renaissance for regulatory peptides. In this perspective, we review what we have learned from the pioneers in exemplified fields of gut peptides, such as cholecystokinin, enterochromaffin‐like‐cell peptides, and glucagon, from the trailblazing studies on the key stress hormone, corticotropin‐releasing factor, as well as from more recently characterized relaxin‐family peptides and receptors. The historical viewpoints are based on our understanding of these topics in light of the earliest phases of research and on subsequent studies and the evolution of knowledge, aiming to sharpen our vision of the current state‐of‐the‐art and those studies that should be prioritized in the future.

“…Cerebral gliomas, astrocytomas, and acoustic neuromas also express CCK peptides (136)(137)(138). The present knowledge about tumor expression of CCK has been summarized in a recent review that also discusses measurements of CCK and proCCK in plasma as tumor markers (139).…”

Section: Cck In Tumor Cellsmentioning

confidence: 99%

Cholecystokinin and the hormone concept

2021

Endocrine Connections

Self Cite

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.