Characterization, in some human breast cancer cell lines, of gastrin‐releasing peptide‐like receptors which are absent in normal breast epithelial cells

Giacchetti, Sylvie; Gauville, C; Crémoux, Patricia de; Bertin, Lise; Berthon, Philippe; Abita, Jean Pierre; Cuttitta, Frank; Calvo, Fabien

doi:10.1002/ijc.2910460226

Cited by 86 publications

(79 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…GRPR activation has been shown to stimulate cancer cell proliferation, whereas GRPR antagonists to reduce tumor growth in a range of experimental cancer models (1,2). In gynecologic cancers, GRPR is likely to be highly expressed in breast, ovarian and cervical tumors, as well as in breast cancer cell lines, whereas its expression is low or absent in non-neoplastic tissue and healthy cells (1,(3)(4)(5)(6)(7)(8). The pharmacological blockade of GRPR by synthetic peptides acting as selective antagonists (RC-3940-II, RC-3095) has been shown to reduce human breast and ovarian tumor growth xenografted into nude mice (9)(10)(11).…”

Section: Introductionmentioning

confidence: 99%

Influence of GRPR and BDNF/TrkB signaling on the viability of breast and gynecologic cancer cells

Cornélio

Farias

Prusch

et al. 2012

Molecular and Clinical Oncology

View full text Add to dashboard Cite

Abstract. Neuropeptide and neurotrophin receptors are increasingly important molecular targets in cancer. Scientific findings indicate that compounds blocking gastrin-releasing peptide receptors (GRPR) or tropomyosin receptor kinase (Trk) receptors are likely to have antiproliferative activities against cancer cells. The present study aimed to demonstrate that, in contrast to previous findings, GRPR activation reduces, whereas its blockade increases the viability of breast, ovarian and cervical cancer cell lines. However, consistent with previous studies, Trk inhibition was demonstrated to reduce the viability of these cells. MCF-7 (breast), OVCAR-3 (ovarian) and HeLa (cervical) human cancer cell lines were treated with GRP, the GRPR antagonists RC-3095 and RC-3940-II, brain-derived neurotrophic factor (BDNF) and the Trk antagonist K252α. Cell viability was measured by the MTT assay. Expression of GRPR and BDNF was confirmed with reverse transcription-polymerase chain reaction (RT-PCR). GRP reduced, whereas RC-3940-II enhanced the viability of the three cell lines. Treatment with K252α inhibited the viability of the cell lines, while BDNF increased the viability of OVCAR-3 cells. The results supported the hypothesis that GRPR and BDNF/TrkB signaling regulates cancer cell viability. Most importantly, these findings are the first to demonstrate that GRPR blockade can stimulate, rather than inhibits the viability of breast and gynecologic cancer cell lines.

show abstract

Section: Introductionmentioning

confidence: 99%

Influence of GRPR and BDNF/TrkB signaling on the viability of breast and gynecologic cancer cells

Cornélio

Farias

Prusch

et al. 2012

Molecular and Clinical Oncology

View full text Add to dashboard Cite

show abstract

“…Yet little is known about the mechanism(s) whereby this receptor can cause the proliferation of human colon cancers. In many other human cancers GRP can act as a mitogen including adenocarcinoma cell lines of the breast (18) and prostate (19,20), as well as in all small cell lung cancer cell lines studied to date (21,22). In small cell lung cancer, tumor cells express GRP-R and secrete GRP, allowing this peptide to act as an autocrine growth factor (21).…”

Section: Introductionmentioning

confidence: 99%

Constitutive activation of the gastrin-releasing peptide receptor expressed by the nonmalignant human colon epithelial cell line NCM460.

Ferris¹,

Carroll²,

Rasenick³

et al. 1997

J. Clin. Invest.

View full text Add to dashboard Cite

Gastrin-releasing peptide (GRP) causes multiple effects in humans by activating a specific heptaspanning receptor. Within the gastrointestinal tract, GRP receptors (GRP-R) are not normally expressed by mucosal epithelial cells except for those lining the gastric antrum. In contrast, recent studies have shown that up to 40% of resected colon cancers aberrantly express this receptor. This is important because the GRP-R can cause the proliferation of many, but not all, tissues in which it is expressed. Since GRP and other agonists are not known to exist in the colonic lumen, it has not been clear how or even if GRP-R expression in colon cancer contributes to cell proliferation. To evaluate the functional consequence of GRP-R expression on colonic epithelium, we transfected the recently isolated nonmalignant human colon epithelial cell line NCM460 with the cDNA for this receptor. All NCM460 cell lines expressing varying numbers of GRP-R bound selected agonists and antagonists indistinguishably from receptors expressed by other human tissues. Furthermore GRP-R-expressing transfected cell lines, but not wild-type NCM460 cells, proliferated independently of serum or other growth factors. Further evaluation revealed that GRP-R in these cells tonically stimulated G ␣ q/11, resulting in increased phospholipase C activation. Since transfected cells do not secrete GRP, nor is their growth influenced by exposure to receptor-specific antagonists, these data indicate that GRP-R ectopically expressed by NCM460 cells are constitutively active. This report provides the first evidence of mutation-independent heptaspanning receptor constitutive activation resulting in cell proliferation, and identifies a potential mechanism whereby the GRP-R may act as an oncogene in human colon cancer. ( J. Clin. Invest. 1997. 100: 2530-2537.)

show abstract

“…Gastrin-releasing peptide mediates its action through specific membrane-bound receptors. The presence of bombesin/GRP receptors on the surface of breast cancer cells has been described (Giacchetti et al, 1990;De Jong et al, 1998a). In this regard, a significantly higher percentage of receptor-positive cases could be identified by autoradiography (Gugger and Reubi, 1999), compared with binding studies in cell lines, in which a 33% incidence of GRP receptor-positive breast carcinomas was found.…”

mentioning

confidence: 99%

Bombesin antagonists inhibit proangiogenic factors in human experimental breast cancers

et al. 2004

View full text Add to dashboard Cite

The overexpression of angiogenic factors such as vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF) and insulin-like growth factors (IGFs) plays a role in the migration and proliferation of endothelial cells in many cancers. Consequently, we investigated the effects of bombesin/gastrin-releasing peptide (GRP) antagonists on the expression of these angiogenic factors, the activities of matrix metalloproteinases (MMPs)-2 and -9, as well as the vascular density in MDA-MB-435 human oestrogenindependent breast cancers. Nude mice bearing orthotopic xenografts of MDA-MB-435 breast cancers were treated with bombesin/ GRP antagonists for 6 weeks. Daily administration of 20 mg of RC-3095 or 10 mg of RC-3940-II significantly decreased the weight of MDA-MB-435 cancers by 44 and 53%, respectively. The inhibition of tumour growth was associated with a substantial reduction in the expression of mRNA and protein levels of basic fibroblast growth factor (bFGF), IGF-II and VEGF-A in the tumours. Both bombesin/GRP antagonists significantly decreased the vessel density of the tumours by about 37%, as shown by immunohistochemical detection of vessels on tumour slides. Gelatinolytic activities, detected by zymography, revealed a 33 -46% reduction in MMP-9 activity after the treatment with either antagonist. In vitro studies revealed that MDA-MB-435 cells secrete bFGF, IGF-II and VEGF-A, and the secretion of these factors is inhibited by RC-3095 and RC-3940-II. This study demonstrates the antiangiogenic effect of bombesin/GRP antagonists RC-3095 and RC-3940-II, and underscores their possible therapeutic application for treatment of breast cancers.

show abstract

Characterization, in some human breast cancer cell lines, of gastrin‐releasing peptide‐like receptors which are absent in normal breast epithelial cells

Cited by 86 publications

References 38 publications

Influence of GRPR and BDNF/TrkB signaling on the viability of breast and gynecologic cancer cells

Influence of GRPR and BDNF/TrkB signaling on the viability of breast and gynecologic cancer cells

Constitutive activation of the gastrin-releasing peptide receptor expressed by the nonmalignant human colon epithelial cell line NCM460.

Bombesin antagonists inhibit proangiogenic factors in human experimental breast cancers

Contact Info

Product

Resources

About