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.