Recombinant C-terminal fragments of the gastrin-releasing peptide precursor are bioactive

C-terminal fragments from the precursor for gastrin-releasing peptide (GRP) have been detected in several human tumour types. We have previously demonstrated that recombinant human proGRP42-98 is biologically active. To investigate the regions responsible, proGRP42-98 was cleaved with thrombin, and the fragments purified by HPLC. Both proGRP42-79 and proGRP80-98 stimulated proliferation of the human colorectal carcinoma cell line DLD-1, but neither peptide bound to the GRP receptor or bombesin receptor subtype 3. We conclude that two distinct regions of the proGRP C-terminus are biologically active, via a receptor distinct from the known GRP receptors. This discovery opens the way for the development of selective antagonists that may offer new therapies for proGRP-producing tumours.

Patel et al. Cancer Lett. 2007 Aug 28;254(1):87-93.

Gastrin releasing peptide and gastrin releasing peptide receptor expression in gastrointestinal carcinoid tumours

Aims: To establish whether gastrin releasing peptide (GRP) and the GRP receptor (GRPR) are expressed together in gastrointestinal carcinoid tumours.

Methods: Twenty six carcinoid tumours from the stomach, small intestine, appendix, and colorectum were investigated by immunohistochemistry for GRP and GRPR.

Results: GRP was detected in nine of 19 tumours and GRPR in 22 of 26. Coexpression of both the ligand and receptor was seen in six of 19 cases. GRPR but not GRP was more strongly expressed in appendix and colonic tumours.

Conclusions: GRP and GRPR are produced by a large number of gastrointestinal carcinoid tumours. An autocrine/paracrine pathway may exist for GRP stimulated cell proliferation in some of these neoplasms, analogous to that seen in small cell anaplastic carcinoma of the lung.

Scott et al. J Clin Pathol. 2004 February; 57(2): 189–192.

Plasma gastrin response with and without BIM 26226

Plasma gastrin responses before, during, and after intragastric instillation of an acidified liquid meal with and without concomitant intravenous BIM26226 in six healthy subjects. Basal as well as meal stimulated gastrin release were not significantly changed by BIM26226.

Hildebrand et al. Gut. 2001 Jul;49(1):23-8.

Mapping in Human Colon/Stomach Tissue (H-027-07)

Protocol for Immunohistochemistry

Mapping in Human Colon/Stomach Tissue (H-027-13)

Protocol for Immunohistochemistry

Mapping in Human Lung Cancer Tissue (H-027-36)

Protocol for Immunohistochemistry

Expression of gastrin-releasing peptide (GRP) in neuroblastomas

Expression of gastrin-releasing peptide (GRP) in neuroblastomas. Representative histologic sections of immunohistochemical staining with GRP antibody in neuroblastomas compared with ganglioneuromas (×100). Large mature ganglion cells show GRP protein (brown staining) in the cytoplasm.

Kim et al. Ann Surg. 2002 May; 235(5): 621–630.