Pro-gastrin-releasing-peptide, also known as Pro-GRP, is a gastrin-releasing peptide (GRP) precursor, a neurotransmitter that belongs to the bombesin-related neuromedin B family. GRP stimulates the secretion of gastrin in order to increase the acidity of the gastric acid. Pro-GRP is a peptide composed of 125 amino acids, expressed in the nervous system and digestive tract. [1] [2] It is different from progastrin, consisting of 80 amino acids, precursor of gastrin in its intracellular version and oncogene in its extracellular version (hPG80). [3] [4]
The presence of GRP in lung cancer samples was identified in 1983. [5] In pathological situations, GRP has mitogenic activity in vitro in many cancers including pancreatic cancer, small cell lung carcinoma, prostate cancer, kidney cancer, breast and colorectal cancer. [6] [7] [8] [9] GRP could operate as an autocrine growth factor. In cancers, GRP induces cell growth and inhibits apoptosis by shutting down the endoplasmic reticulum stress pathway. [10] The mechanisms of the impacted signal pathways have not been established. [11] As early as 1994, research on Pro-GRP as a biomarker for small-cell lung carcinoma began. [12] Because of the very short half-life of GRP (2 minutes), the Pro-GRP is used for measurements and analysis. Since then, Pro-GRP has been used as a tumor marker for patients with small-cell lung carcinoma in limited and extended stages. [13]
Substance P (SP) is an undecapeptide and a type of neuropeptide, belonging to the tachykinin family of neuropeptides. It acts as a neurotransmitter and a neuromodulator. Substance P and the closely related neurokinin A (NKA) are produced from a polyprotein precursor after alternative splicing of the preprotachykinin A gene. The deduced amino acid sequence of substance P is as follows:
Gastrin is a peptide hormone that stimulates secretion of gastric acid (HCl) by the parietal cells of the stomach and aids in gastric motility. It is released by G cells in the pyloric antrum of the stomach, duodenum, and the pancreas.
Bombesin is a 14-amino acid peptide originally isolated from the skin of the European fire-bellied toad by Vittorio Erspamer et al. and named after its source. It has two known homologs in mammals called neuromedin B and gastrin-releasing peptide. It stimulates gastrin release from G cells. It activates three different G-protein-coupled receptors known as BBR1, -2, and -3. It also activates these receptors in the brain. Together with cholecystokinin, it is the second major source of negative feedback signals that stop eating behaviour.
Neuroendocrine cells are cells that receive neuronal input and, as a consequence of this input, release messenger molecules (hormones) into the blood. In this way they bring about an integration between the nervous system and the endocrine system, a process known as neuroendocrine integration. An example of a neuroendocrine cell is a cell of the adrenal medulla, which releases adrenaline to the blood. The adrenal medullary cells are controlled by the sympathetic division of the autonomic nervous system. These cells are modified postganglionic neurons. Autonomic nerve fibers lead directly to them from the central nervous system. The adrenal medullary hormones are kept in vesicles much in the same way neurotransmitters are kept in neuronal vesicles. Hormonal effects can last up to ten times longer than those of neurotransmitters. Sympathetic nerve fiber impulses stimulate the release of adrenal medullary hormones. In this way the sympathetic division of the autonomic nervous system and the medullary secretions function together.
Gastrin-releasing peptideGRP, is a neuropeptide, a regulatory molecule encoded in the human by the GRP gene. GRP has been implicated in a number of physiological and pathophysiological processes. Most notably, GRP stimulates the release of gastrin from the G cells of the stomach.
Gastrinomas are neuroendocrine tumors (NETs), usually located in the duodenum or pancreas, that secrete gastrin and cause a clinical syndrome known as Zollinger–Ellison syndrome (ZES). A large number of gastrinomas develop in the pancreas or duodenum, with near-equal frequency, and approximately 10% arise as primary neoplasms in lymph nodes of the pancreaticoduodenal region.
Enteroendocrine cells are specialized cells of the gastrointestinal tract and pancreas with endocrine function. They produce gastrointestinal hormones or peptides in response to various stimuli and release them into the bloodstream for systemic effect, diffuse them as local messengers, or transmit them to the enteric nervous system to activate nervous responses. Enteroendocrine cells of the intestine are the most numerous endocrine cells of the body. They constitute an enteric endocrine system as a subset of the endocrine system just as the enteric nervous system is a subset of the nervous system. In a sense they are known to act as chemoreceptors, initiating digestive actions and detecting harmful substances and initiating protective responses. Enteroendocrine cells are located in the stomach, in the intestine and in the pancreas. Microbiota play key roles in the intestinal immune and metabolic responses in these enteroendocrine cells via their fermentation product, acetate.
Neprilysin is an enzyme that in humans is encoded by the MME gene. Neprilysin is a zinc-dependent metalloprotease that cleaves peptides at the amino side of hydrophobic residues and inactivates several peptide hormones including glucagon, enkephalins, substance P, neurotensin, oxytocin, and bradykinin. It also degrades the amyloid beta peptide whose abnormal folding and aggregation in neural tissue has been implicated as a cause of Alzheimer's disease. Synthesized as a membrane-bound protein, the neprilysin ectodomain is released into the extracellular domain after it has been transported from the Golgi apparatus to the cell surface.
H1299, also known as NCI-H1299 or CRL-5803, is a human non-small cell lung carcinoma cell line derived from the lymph node, which is widely used in research.
The bombesin receptor subtype 3 also known as BRS-3 or BB3 is a protein which in humans is encoded by the BRS3 gene.
The neuromedin B receptor (NMBR), now known as BB1 is a G protein-coupled receptor whose endogenous ligand is neuromedin B. In humans, this protein is encoded by the NMBR gene.
The gastrin-releasing peptide receptor (GRPR), now properly known as BB2 is a G protein-coupled receptor whose endogenous ligand is gastrin releasing peptide. In humans it is highly expressed in the pancreas and is also expressed in the stomach, adrenal cortex and brain.
Neuropilin-1 is a protein that in humans is encoded by the NRP1 gene. In humans, the neuropilin 1 gene is located at 10p11.22. This is one of two human neuropilins.
Combined small cell lung carcinoma is a form of multiphasic lung cancer that is diagnosed by a pathologist when a malignant tumor, arising from transformed cells originating in lung tissue, contains a component of small cell lung carcinoma (SCLC) mixed with one or more components of any histological variant of non-small cell lung carcinoma (NSCLC) in any relative proportion.
Large cell lung carcinoma with rhabdoid phenotype (LCLC-RP) is a rare histological form of lung cancer, currently classified as a variant of large cell lung carcinoma (LCLC). In order for a LCLC to be subclassified as the rhabdoid phenotype variant, at least 10% of the malignant tumor cells must contain distinctive structures composed of tangled intermediate filaments that displace the cell nucleus outward toward the cell membrane. The whorled eosinophilic inclusions in LCLC-RP cells give it a microscopic resemblance to malignant cells found in rhabdomyosarcoma (RMS), a rare neoplasm arising from transformed skeletal muscle. Despite their microscopic similarities, LCLC-RP is not associated with rhabdomyosarcoma.
Bombesin-like peptides comprise a large family of peptides which were initially isolated from amphibian skin, where they stimulate smooth muscle contraction. They were later found to be widely distributed in mammalian neural and endocrine cells.
Local hormones are a large group of signaling molecules that do not circulate within the blood. Local hormones are produced by nerve and gland cells and bind to either neighboring cells or the same type of cell that produced them. Local hormones are activated and inactivated quickly. They are released during physical work and exercise. They mainly control smooth and vascular muscle dilation. Strength of response is dependent upon the concentration of receptors of target cell and the amount of ligand.
Neuroendocrine differentiation is a term primarily used in relation to prostate cancers that display a significant neuroendocrine cell population on histopathological examination. These types of prostate cancer comprise true neuroendocrine cancers, such as small cell carcinoma, carcinoid and carcinoid-like tumors, as well as prostatic adenocarcinoma exhibiting focal neuroendocrine phenotype.
Progastrin is an 80-amino acid intracellular protein and the precursor of gastrin, a gastrointestinal hormone produced by G cells in the gastric antrum. The main function of gastrin is to regulate acid secretion. During digestion, only gastrin is released into the bloodstream and stimulates the secretion of hydrochloric acid in the stomach as well as pancreatic digestive enzymes. In humans, progastrin is encoded by the GAST gene. Progastrin is expressed primarily in stomach tissue.
hPG80 refers to the extracellular and oncogenic version of progastrin. This name first appeared in a scientific publication in January 2020. Until that date, scientific publications only mention 'progastrin', without necessarily explicitly specifying whether it is intracellular or extracellular in the tumor pathological setting.