scholarly journals Increased gastrin-releasing peptide (GRP) receptor expression in tumour cells confers sensitivity to [Arg6,D-Trp7,9,NmePhe8]-substance P (6–11)-induced growth inhibition

2003 ◽  
Vol 88 (11) ◽  
pp. 1808-1816 ◽  
Author(s):  
C M Waters ◽  
A C MacKinnon ◽  
J Cummings ◽  
U Tufail-Hanif ◽  
D Jodrell ◽  
...  
2013 ◽  
Vol 109 (3) ◽  
pp. 742-748 ◽  
Author(s):  
Tasuku Akiyama ◽  
Mitsutoshi Tominaga ◽  
Auva Davoodi ◽  
Masaki Nagamine ◽  
Kevin Blansit ◽  
...  

Recent studies support roles for neurokinin-1 (NK-1) and gastrin-releasing peptide (GRP) receptor-expressing spinal neurons in itch. We presently investigated expression of substance P (SP) and GRP in pruritogen-responsive primary sensory neurons and roles for these neuropeptides in itch signaling. Responses of dorsal root ganglion (DRG) cells to various pruritogens were observed by calcium imaging. DRG cells were then processed for SP, GRP, and isolectin B-4 (IB4; a marker for nonpeptidergic neurons) immunofluorescence. Of pruritogen-responsive DRG cells, 11.8–26.8%, 21.8–40.0%, and 21.4–26.8% were immunopositive for SP, GRP, and IB4, respectively. In behavioral studies, both systemic and intrathecal administration of a NK-1 receptor antagonist significantly attenuated scratching evoked by chloroquine and a protease-activated receptor 2 agonist, SLIGRL, but not histamine, bovine adrenal medulla peptide 8-22 (BAM8-22), or serotonin. Systemic or intrathecal administration of a GRP receptor antagonist attenuated scratching evoked by chloroquine and SLIGRL but not BAM8-22 or histamine. The GRP receptor antagonist enhanced scratching evoked by serotonin. These results indicate that SP and GRP expressed in primary sensory neurons are partially involved as neurotransmitters in histamine-independent itch signaling from the skin to the spinal cord.


2007 ◽  
Vol 29 (5) ◽  
pp. 421-433 ◽  
Author(s):  
Achim Fleischmann ◽  
Beatrice Waser ◽  
Jean Claude Reubi

Background: Peptide receptors, overexpressed in specific cancers, represent new diagnostic and therapeutic targets. In this study, receptors for the gastrin-releasing peptide (GRP), and other members of the bombesin-family of peptides, were evaluated in ovarian neoplasms. Methods: 75 primary, secondary and metastatic ovarian tumors were investigated for their bombesin-receptor subtype expression, incidence, localization and density using in vitro autoradiography on tissue sections with the universal radioligand 125I-[D-Tyr6, ß-Ala11, Phe13, Nle14]-bombesin(6-14) and the GRP-receptor subtype-preferring 125I-[Tyr4]-bombesin. Results: GRP-receptors were detected in 42/61 primary ovarian tumors; other bombesin-receptor subtypes (BB1, bb3) were rarely present (3/61). Two different tissue compartments expressed GRP-receptors: the tumoral vasculature was the predominant site of GRP-receptor expression (38/61), whereas neoplastic cells more rarely expressed GRP-receptors (14/61). GRP-receptor positive vessels were present in the various classes of ovarian tumors; generally, malignant tumors had a higher incidence of GRP-receptor positive vessels compared to their benign counterparts. The prevalence of such vessels was particularly high in ovarian carcinomas (16/19) and their metastases (5/5). The GRP-receptors were expressed in high density in the muscular vessel wall. Normal ovary (n=10) lacked GRP-receptors. Conclusions: The large amounts of GRP-receptors in ovarian tumor vessels suggest a role in tumoral vasculature and possibly angiogenesis. Further, these vessels might be targeted in vivo with bombesin analogs for diagnosis or for therapy.


2009 ◽  
Vol 16 (2) ◽  
pp. 623-633 ◽  
Author(s):  
Achim Fleischmann ◽  
Beatrice Waser ◽  
Jean Claude Reubi

Tumoral gastrin-releasing peptide (GRP) receptors are potential targets for diagnosis and therapy using radiolabeled or cytotoxic GRP analogs. GRP-receptor overexpression has been detected in endocrine-related cancer cells and, more recently, also in the vascular bed of selected tumors. More information on vascular GRP-receptors in cancer is required to asses their potential for vascular targeting applications. Therefore, frequent human cancers (n=368) were analyzed using in vitro GRP-receptor autoradiography on tissue sections with the 125I-[Tyr4]-bombesin radioligand and/or the universal radioligand 125I-[d-Tyr6, β-Ala11, Phe13, Nle14]-bombesin(6–14). GRP-receptor expressing vessels were evaluated in each tumor group for prevalence, quantity (vascular score), and GRP-receptor density. Prevalence of vascular GRP-receptors was variable, ranging from 12% (prostate cancer) to 92% (urinary tract cancer). Different tumor types within a given site had divergent prevalence of vascular GRP-receptors (e.g. lung: small cell cancer: 0%; adenocarcinoma: 59%; squamous carcinoma: 83%). Also the vascular score varied widely, with the highest score in urinary tract cancer (1.69), moderate scores in lung (0.91), colon (0.88), kidney (0.84), and biliary tract (0.69) cancers and low scores in breast (0.39) and prostate (0.14) cancers. Vascular GRP-receptors were expressed in the muscular vessel wall in moderate to high densities. Normal non-neoplastic control tissues from these organs lacked vascular GRP-receptors. In conclusion, tumoral vessels in all evaluated sites express GRP-receptors, suggesting a major biological function of GRP-receptors in neovasculature. Vascular GRP-receptor expression varies between the tumor types indicating tumor-specific mechanisms in their regulation. Urinary tract cancers express vascular GRP-receptors so abundantly, that they are promising candidates for vascular targeting applications.


2015 ◽  
Vol 74 (Suppl 2) ◽  
pp. 218.1-218
Author(s):  
V.S. Clarimundo ◽  
M. Farinon ◽  
C. Nör ◽  
L.I. Filipin ◽  
P.S. Gulko ◽  
...  

2008 ◽  
Vol 102 (11) ◽  
pp. 1154-1156 ◽  
Author(s):  
Alexandre B.M. da Silveira ◽  
Michelle A.R. Freitas ◽  
Enio C. de Oliveira ◽  
Salustiano G. Neto ◽  
Alejandro O. Luquetti ◽  
...  

2005 ◽  
Author(s):  
◽  
Christopher Todd Winkelmann

[ACCESS RESTRICTED TO THE UNIVERSITY OF MISSOURI AT AUTHOR'S REQUEST.] Non-invasive imaging techniques have been recently developed to characterize animal models of disease. The overarching hypothesis of this work explores the use of three micro-imaging modalities, including Micro-CT, PET and SPECT, to characterize tumor anatomical progression, metabolism, bone lesion remodeling, and/or gastrin releasing peptide receptor expression in mouse models of metastatic melanoma and prostate and breast cancer bone metastasis. Micro-CT was shown to provide excellent anatomical information about tumor progression in several different tissues including lung, bone, and subcutaneous tissues. Micro-PET imaging demonstrated increased tumor metabolism in melanoma tumors, but was not able to discern bone remodeling in breast cancer bone lesions. Micro-SPECT imaging demonstrated gastrin-releasing peptide receptor expression in a prostate cancer bone metastasis model. The results from this work demonstrate the ability of micro-imaging technologies to non-invasively probe mouse models of disease to obtain information in vivo that is not possible with ex vivo experimental techniques.


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