High-affinity binding sites for gastrin-releasing peptide on human colorectal cancer tissue but not uninvolved mucosa

Abstract

S_mary Human colorectal cancer tissue and matched uninvolved mucosa from 21 patients were examined by radioligand displacement for the presence of binding sites for bombesin-like peptides. Five cancers, but no univolved mucosa, expressed high-affinity, low-capacity bombesin binding sites (KYd = 6.53 nM, B.. = 58.6 fmol mg-' protein) of the gastrin-releasing peptide (GRP)-preferring subtype (IC50 4.8 nM).Bombesin-like peptides may have a role in the pathogenesis of colorectal cancer, and bombesin receptor antagonists may be of value in the treatment of receptor-positive tumours.

Bombesin family receptor and ligand gene expression in human colorectal cancer and normal mucosa

“…We have previously shown, by means of radioligand binding studies, that GRP receptors are expressed in 24% of colorectal cancers (Preston et al, 1995), which is in agreement with previous reports (Radulovic et al, 1992). These binding sites are not detected in normal colonic mucosa.…”

“…Our finding that GRP receptor mRNA is expressed in colonic epithelium is at variance with a recent report (Ferris et al, 1997). The absence of expression of NMB receptor mRNA demonstrated in this study is consistent with our studies using radioligand binding (Preston et al, 1995) where GRP receptor but not NMB receptor expression was demonstrated in tumour.…”

“…Using RT-PCR the GRP receptor appears to be reliably over expressed in at least 70% of colorectal cancers when compared with uninvolved mucosa. Previous radioligand binding studies demonstrated that about 25-40% of cancers express the GRP receptor (Radulovic et al, 1991;Preston et al, 1995), but it is undetectable in normal mucosa. One possible explanation is that the low level of expression of the GRP-R by the mucosa was not detectable above the background in the radioligand assays but was detectable in this study by the more sensitive RT-PCR.…”

Bombesin induces cyclooxygenase-2 expression through the activation of the nuclear factor of activated T cells and enhances cell migration in Caco-2 colon carcinoma cells

“…Aberrant expression of Cox-2, BBS/GRP and GRP-R has been observed in a variety of tumors, including colorectal carcinomas (Preston et al, 1995;Carroll et al, 1999Carroll et al, , 2000Gupta and Dubois, 2001;Jensen et al, 2001) and several lines of evidence suggest a link among these proteins in cancer progression (Hecht et al, 1997;Guo et al, 2001;Iishi et al, 2003). We have analysed the potential association between BBS-mediated signaling and Cox-2 in colon carcinoma cells, demonstrating that BBS stimulation of Caco-2 cells leads to a rapid upregulation of Cox-2 expression at both mRNA and protein levels resulting in increased production of PGE 2 .…”

“…Even more, GRP and its cognate G-protein-coupled receptor (GRP-R), as well as Cox-2, are overexpressed in a substantial fraction of human colorectal carcinomas (38-76% ) (Preston et al, 1995;Carroll et al, 1999Carroll et al, , 2000Gupta and Dubois, 2001;Jensen et al, 2001). BBS/GRP are neurotransmitters expressed mainly in nerve fibers throughout the mammalian gut and in the central nervous system.…”