Gastrin‐releasing peptide: Different forms, different functions

Abstract

All forms of the neuropeptide gastrin-releasing peptide (GRP) are derived from the precursor proGRP1-125. Amidated GRP18-27, which together with amidated GRP1-27 was long thought to be the only biologically relevant product of the GRP gene, is involved in a multitude of physiological functions and acts as a mitogen, morphogen, and proangiogenic factor in certain cancers. Recently, GRP has been implicated in several psychiatric conditions, in the maintenance of circadian rhythm, in spinal transmission of the itch sensation, and in inflammation and wound repair. The actions of GRP are mediated by the GRP receptor. Over the last decade, nonamidated peptides derived from proGRP, such as the glycine-extended form GRP18-28 and recombinant and synthetic fragments from proGRP31-125, have been shown to be biologically active in a range of tissues and in cancer cell lines. While GRP18-28 acts via the GRP receptor, the identity of the receptor for proGRP31-125 and its fragments has not yet been established. Nonamidated fragments are also present in normal tissues and in various cancers. In fact, proGRP31-98 is the most sensitive serum biomarker in patients with small cell lung cancer and is a significant predictor of poor survival in patients with advanced prostate cancer.

Selective capacity of metreleptin administration to reconstitute CD4 + T-cell number in females with acquired hypoleptinemia

“…This receptor lacks a cytoplasmic death domain and hence is not capable of inducing apoptosis; rather, it protects against TRAILmediated apoptosis by competing with TRAIL-R1 and -R2 for binding to the ligand. The hormone gastrin also was up-regulated, whereas both interleukin enhancer-binding factor-2 (ILF-2) and the growth factor-independent 1 (GFI-1) transcription repressor were down-regulated (26,27). The following factors are involved directly and indirectly in lymphocyte survival and function: (i) gastrin, in addition to its effect on acid secretion by gastric cells, has hematopoietic and proinflammatory activities (28); (ii) ILF-2 encodes for a nuclear factor of activated T cells (NFAT) required for T-cell expression of the IL-2 gene (29); and (iii) GFI-1 encodes a nuclear zinc finger protein that functions as a transcriptional repressor (30).…”

Significance of gastrin-releasing peptide in ovarian cancer ES2 cells

“…GRP and its receptor, GRPR, are overexpressed in a number of different tumors, and are believed to have an important role in carcinogenesis and tumor progression (12). It has been hypothesized that the carcinogenic ability of GRP relies on its affinity to GRPR.…”

Gastrin-releasing peptide links stressor to cancer progression

“…Chronic administration of GRP induced gastric and pancreatic hyperplasia in vivo and induced Swiss 3T3 Wbroblast or human bronchial epithelial cell proliferations in vitro (Lehy et al 1983;Rozengurt and Sinnett-Smith 1983;Willey et al 1984;Hajri et al 1992). Further studies demonstrated that both amidated and nonamidated forms of GRP accelerated the proliferation and migration of human cancer cells in vitro (Dumesny et al 2006;Gonzalez et al 2008;Ischia et al 2009). It is reported that GRP and GRPR often co-expressed in human cancers, and GRP directly binds to its high-aYnity receptor to establish autocrine or paracrine growth loops (Fig.…”

“…However, the distribution of GRPR is not well determined; it was reported that GRPR expressed in limited human tissues including pancreas, stomach, adrenal cortex, and brain (Xiao et al 2001). The most important physiological functions of GRP include sensory transmission, regulation of central autonomic pathways, thermoregulation, secretion of pituitary hormones, gastric and pancreatic secretion, and food intake and satiety (Panula 1986;Gonzalez et al 2008;Ischia et al 2009). …”

“…The cDNA encoding human GRP was Wrst cloned from the hepatic metastasis of a pulmonary carcinoma, and the gene was mapped to chromosome 18q21 (Spindel et al 1984). Further studies revealed that there are three isoforms of GRP in humans: GRP1-27, GRP18-27, and GRP18-27gly, all are generated by processing of a larger precursor peptide progastrin-releasing peptide (proGRP) (Dumesny et al 2006;Ischia et al 2009). It is suggested that GRP binds to its high-aYnity receptor (gastrin-releasing peptide receptor, GRPR) in a paracrine, autocrine, or neurocrine manners to regulate cellular functions (Gonzalez et al 2008).…”