Expression and Role of GPR87 in Urothelial Carcinoma  of the Bladder

Okazoe, Homare; Zhang, Xia; Liu, Dage; Shibuya, Shinsuke; Ueda, Nobufumi; Sugimoto, Mikio; Kakehi, Yoshiyuki

doi:10.3390/ijms140612367

Cited by 14 publications

(17 citation statements)

References 23 publications

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“…Regarding the biological properties of GPR87 in NSCLC, the present study demonstrated that GPR87 expression was correlated with tumor proliferation. The Ki-67 proliferation index was significantly higher in GPR87-positive compared to that in GPR87-negative tumors, which was consistent with the findings of a recent study on bladder carcinoma (16). Furthermore, with the use of serial sections, the Ki-67 immunostaining pattern was found to be immunohistochemically identical to that of GPR87 in the majority of the tumor samples (Fig.…”

Section: Discussionsupporting

confidence: 90%

Overexpression of G protein-coupled receptor 87 correlates with poorer tumor differentiation and higher tumor proliferation in non-small-cell lung cancer

Nii

Tokunaga

Liu

et al. 2014

Molecular and Clinical Oncology

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Abstract. G protein-coupled receptor 87 (GPR87) is a newly deorphanized member of the transmembrane G protein-coupled receptor family. Recently, GPR87 was suggested to contribute to the viability of human tumor cells and overexpression of GPR87 mRNA was detected in a number of malignant tumors, including lung cancer. We performed a retrospective study of GPR87 expression in association with clinical characteristics and biological markers in non-small-cell lung cancer (NSCLC). We investigated a total of 123 patients with NSCLC who underwent surgery between 1999 and 2004 (58 adenocarcinomas, 53 squamous cell carcinomas and 12 others). Immunohistochemistry was used to evaluate the intratumoral expression of GPR87 and the Ki-67 proliferation index. The TUNEL method was also used to investigate tumor apoptosis. A total of 63 tumors (51.2%) were found to be GPR87-positive. These tumors were more frequently encountered among squamous cell carcinomas rather than among adenocarcinomas (62.3 vs. 43.1%, respectively; P=0.044) and were significantly more frequently poorly and moderately differentiated rather than well differentiated (P=0.029). Moreover, the Ki-67 index was significantly higher in GPR87-positive compared to GPR87-negative tumors (57.0 vs. 40.0%, respectively; P=0.002). The overall survival was significantly worse for patients with GPR87-positive compared to those with GPR87-negative tumors (P=0.029). The Cox regression analyses also demonstrated that the GPR87 status was a significant prognostic factor for NSCLC patients [hazard ratio=2.053; P=0.018). The present study demonstrated that in NSCLC, the overexpression of GPR87 is significantly associated with poorer differentiation and higher proliferation. During the progression of NSCLC, GPR87 overexpression may be associated with the acquisition of a more aggressive phenotype and, therefore, is a potentially useful target for prognostication and treatment.

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Section: Discussionsupporting

confidence: 90%

Overexpression of G protein-coupled receptor 87 correlates with poorer tumor differentiation and higher tumor proliferation in non-small-cell lung cancer

Nii

Tokunaga

Liu

et al. 2014

Molecular and Clinical Oncology

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“…Another altered protein, GPR87, is a kind of cell‐surface molecule involved in signal transmission, and plays an essential role in tumor growth (Dorsam & Gutkind, ). Recent studies suggest that the association between GPR87 and tumorigenesis might be related to cancer cell proliferation (Okazoe et al, ; Zhang et al, ). Although the carcinogenic effect of AA was described in 1982, there is no study discussing the association between AA and GPR87 (Mengs, Lang, & Poch, ).…”

Section: Discussionmentioning

confidence: 99%

Proteomics analysis of altered proteins in kidney of mice with aristolochic acid nephropathy using the fluorogenic derivatization–liquid chromatography–tandem mass spectrometry method

Lin

Chang

Lee

et al. 2017

Biomedical Chromatography

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Aristolochic acid (AA) causes interstitial renal fibrosis, called aristolochic acid nephropathy (AAN). There is no specific indicator for diagnosing AAN, so this study aimed to investigate the biomarkers for AAN using a proteomics method. The C3H/He female mice were given ad libitum AA-distilled water (0.5 mg/kg/day) and distilled water for 56 days in the AA and normal groups, respectively. The AA-induced proteins in the kidney were investigated using a proteomics study, including fluorogenic derivatization with 7-chloro-N-[2-(dimethylamino)ethyl]-2,1,3-benzoxadiazole-4-sulfonamide, followed by high-performance liquid chromatography analysis and liquid chromatography tandem mass spectrometry with a MASCOT database searching system. There were two altered proteins, thrombospondin type 1 (TSP1) and G protein-coupled receptor 87 (GPR87), in the kidney of AA-group mice on day 56. GPR87, a tumorigenesis-related protein, is reported for the first time in the current study. The renal interstitial fibrosis was certainly induced in the AA-group mice under histological examination. Based on the results of histological examination and the proteomics study, this model might be applied to AAN studies in the future. TSP1 might be a novel biomarker for AAN, and the further role of GPR87 leading to AA-induced tumorigenesis should be researched in future studies.

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“…An adenoviral vector expressing shRNA expressed under the control of the RNA polymerase III-dependent promoter for supplying stable siRNA molecules was constructed as described previously [ 11 , 29 ]. A control adenoviral vector expressing shRNA against the scramble sequence of GPR87-siRNA (5′-UCUUAAUCGCGUAUAAGGCTT-3′) was also constructed (Ad-scramble).…”

Section: Methodsmentioning

confidence: 99%

“…Use of various mRNA expression databases, laser-capture-microdissected (LCM) tissue samples and immunohistochemistry with a panel of human tumors have demonstrated tumor-specific overexpression of GPR87 in many human cancers, including TCC [ 10 ]. Moreover, our recent clinical study of non-muscle-invasive bladder cancer also showed that GPR87-overexpression was correlated with higher tumor proliferation, and that patients with GPR87-positive tumors had a shorter intravesical recurrence-free survival period [ 11 ]. The precise molecular mechanisms by which GPR87 promotes cell proliferation and contributes to cell viability have not been sufficiently analyzed.…”

Section: Introductionmentioning

confidence: 99%

“…To explore effective gene therapies for GPR87-expressing cancers including urothelial cancer, and to clarify the functional role of GPR87, we constructed an adenoviral vector expressing short hairpin RNA (shRNA) targeting GPR87 (Ad-shGPR87) and confirmed its anti-proliferative effect on an GPR87-expressing bladder cell line HT1197 [ 11 ]. In the present study, we further explored the antitumor activity in more bladder tumor cell lines both in vitro and in vivo and aim to clarify the functional role of GPR87 in bladder cancer.…”

Section: Introductionmentioning

confidence: 99%

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G Protein-Coupled Receptor 87 (GPR87) Promotes Cell Proliferation in Human Bladder Cancer Cells

Zhang

Liu

Hayashida

et al. 2015

IJMS

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G protein-coupled receptor 87 (GPR87) is a newly deorphanized member of the cell surface molecule G protein-coupled receptor family. GPR signaling was shown to play a role in promotion of cell growth and survival, metastasis, and drug resistance. The overexpression of GPR87 has also been reported in many malignant tumors including bladder cancer. The aim of the present study is to examine the effect of silencing GPR87 expression with a replication-deficient recombinant adenoviral vector expressing short hairpin RNA targeting GPR87 (Ad-shGPR87) and to explore the underlying molecular mechanisms in bladder cancer cells. Six GPR87-expressing human bladder cancer cells, HT1197, HT1376, J82, RT112, TCCSUP and UMUC3, were used. Infection with Ad-shGPR87 effectively downregulated the GPR87 expression, and significantly reduced the percentage of viable cells in 4 of 6 cell lines as detected by an MTT assay. Significant inhibition on cell proliferation with Ad-shGPR87 was observed in the wild-type p53 bladder cancer cell lines (HT1197, RT112, TCCSUP and UMUC3), but not in the mutant p53 cells (HT1376 and J82). As represented by a wild-type p53 RT112 cell, Ad-shGPR87 infection significantly enhanced p53 and p21 expression and caused caspase-dependent apoptosis. Furthermore, the treatment with Ad-shGPR87 exerted a significant antitumor effect against the GPR87-expressing RT112 xenografts. GPR87 appeared to be a promising target for gene therapy, and Ad-shGPR87 had strong antitumor effects, specifically anti-proliferative and pro-apoptotic effects, against GPR87-expressing human bladder cancer cells.

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Expression and Role of GPR87 in Urothelial Carcinoma of the Bladder

Cited by 14 publications

References 23 publications

Overexpression of G protein-coupled receptor 87 correlates with poorer tumor differentiation and higher tumor proliferation in non-small-cell lung cancer

Overexpression of G protein-coupled receptor 87 correlates with poorer tumor differentiation and higher tumor proliferation in non-small-cell lung cancer

Proteomics analysis of altered proteins in kidney of mice with aristolochic acid nephropathy using the fluorogenic derivatization–liquid chromatography–tandem mass spectrometry method

G Protein-Coupled Receptor 87 (GPR87) Promotes Cell Proliferation in Human Bladder Cancer Cells

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