CXCR7: A novel tumor endothelial marker in renal cell carcinoma

Maishi, Nako; Ohga, Noritaka; Hida, Yasuhiro; Akiyama, Kosuke; Kitayama, Kenji; Osawa, Takahiro; Onodera, Yuichiro; Shinohara, Nobuo; Nonomura, Katsuya; Shindoh, Masanobu; Hida, Kyoko

doi:10.1111/j.1440-1827.2012.02792.x

Cited by 66 publications

(85 citation statements)

References 42 publications

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“…Similar results were found in the literature from other tumors such as bladder, pancreas, and kidney. [15,40,41] But is partly different from those available, witch CXCR7 were found primarily in endothelial cells of Fig. 4 a CXCR7, b CXCR4 and c HIF1α mRNA expression according IDH1 mutation status.…”

Section: Discussionmentioning

confidence: 94%

CXCR7 and CXCR4 Expressions in Infiltrative Astrocytomas and Their Interactions with HIF1α Expression and IDH1 Mutation

Bianco

Uno

Oba-Shinjo

et al. 2014

Pathol. Oncol. Res.

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The CXCR7, a new receptor for CXCL12 with higher affinity than CXCR4 has raised key issues on glioma cell migration. The aim of this study is to investigate the CXCR7 mRNA expression in diffuse astrocytomas tissues and to evaluate its interactions with CXCR4 and HIF1α expression and IDH1 mutation. CXCR7, CXCR4 and HIF1α mRNA expression were evaluated in 129 frozen samples of astrocytomas. IDH1 mutation status was analyzed with gene expressions, matched with clinicopathological parameters and overall survival time. Protein expression was analyzed by immunohistochemistry in different grades of astrocytoma and in glioma cell line (U87MG) by confocal microscopy. There was significant difference in the expression levels of the genes studied between astrocytomas and non-neoplasic (NN) controls (p < 0.001). AGII showed no significant correlation between CXCR7/HIF1α (p = 0.548); there was significant correlation between CXCR7/CXCR4 (p = 0.042) and CXCR7/IDH1 (p = 0.008). GBM showed significant correlations between CXCR7/CXCR4 (p = 0.002), CXCR7/IDH1 (p < 0.001) and CXCR7/HIF1α (p = 0.008). HIF1α overexpression was associated with higher expressions of CXCR7 (p = 0.01) and CXCR4 (p < 0.0001), while IDH1 mutation was associated with lower CXCR7 (p = 0.009) and CXCR4 (p = 0.0005) mRNA expressions. Protein expression increased with malignancy and in U87MG cell line was mainly localized in the cellular membrane. CXCR7 was overexpressed in astrocytoma and correlates with CXCR4 and IDH1 in AGII and CXCR4, IDH1 and HIF1α in GBM. Overexpression HIF1α was related with higher expressions of CXCR7 and CXCR4, otherwise IDH1 mutation related with lower expression of both genes. No association between CXCR7 and CXCR4 expression and survival data was related.

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Section: Discussionmentioning

confidence: 94%

CXCR7 and CXCR4 Expressions in Infiltrative Astrocytomas and Their Interactions with HIF1α Expression and IDH1 Mutation

Bianco

Uno

Oba-Shinjo

et al. 2014

Pathol. Oncol. Res.

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“…It is also expressed at high levels on tumor-associated vasculature and may have an important role in tumor neovascularization [58]. The role of CXCR7 in cell growth/survival was first suggested by the observation that CXCR7-transfected MDA-MB-435 cells expanded more rapidly in culture and they formed larger tumors than controls in an animal model [55,59].…”

Section: Receptor Trio (Cxcr4 Cxcr7 and Cxcr3) In Cancermentioning

confidence: 99%

“…CXCR4 was highly expressed on the more metastatic alveolar RMS (ARMS) cell line whereas CXCR7 was restricted to non-metastatic cells [62]. Like CXCR4, hypoxia is a major inducer of CXCR7 in tumor cells and tumor-associated endothelial cells emphasizing its role in promoting tumor growth as well as angiogenesis in tumors [58]. …”

Section: Receptor Trio (Cxcr4 Cxcr7 and Cxcr3) In Cancermentioning

confidence: 99%

“…Several lines of evidence indicate that despite being ELR − , CXCL12 promotes angiogenesis via endothelial cell (EC) proliferation, migration, as well as VEGF production [9–11]. Although both CXCR4 and CXCR7 are shown to be moderately expressed in normal EC, the expression of CXCR7 on tumor endothelial cells is markedly upregulated and has recently been proposed as a marker of tumor vasculature in various tumors [58,93]. Hypoxic condition, abundant VEGF and CXCL8 in tumor microenvironment are thought to be the key regulators for the overexpression of CXCR7 in tumor vasculature.…”

Section: Receptor Trio Crosstalk In Cancer Via Shared Ligandsmentioning

confidence: 99%

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Chemokine receptor trio: CXCR3, CXCR4 and CXCR7 crosstalk via CXCL11 and CXCL12

Singh

Arya

Trivedi

et al. 2013

Cytokine & Growth Factor Reviews

171

184

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Although chemokines are well established to function in immunity and endothelial cell activation and proliferation, a rapidly growing literature suggests that CXC Chemokine receptors CXCR3, CXCR4 and CXCR7 are critical in the development and progression of solid tumors. The effect of these chemokine receptors in tumorigenesis is mediated via interactions with shared ligands I-TAC (CXCL11) and SDF-1 (CXCL12). Over the last decade, CXCR4 has been extensively reported to be overexpressed in most human solid tumors and has earned considerable attention toward elucidating its role in cancer metastasis. To enrich the existing armamentarium of anti-cancerous agents, many inhibitors of CXCL12–CXCR4 axis have emerged as additional or alternative agents for neoadjuvant treatments and even many of them are in preclinical and clinical stages of their development. However, the discovery of CXCR7 as another receptor for CXCL12 with rather high binding affinity and recent reports about its involvement in cancer progression, has questioned the potential of “selective blockade” of CXCR4 as cancer chemotherapeutics. Interestingly, CXCR7 can also bind another chemokine CXCL11, which is an established ligand for CXCR3. Recent reports have documented that CXCR3 and their ligands are overexpressed in different solid tumors and regulate tumor growth and metastasis. Therefore, it is important to consider the interactions and crosstalk between these three chemokine receptors and their ligand mediated signaling cascades for the development of effective anti-cancer therapies. Emerging evidence also indicates that these receptors are differentially expressed in tumor endothelial cells as well as in cancer stem cells, suggesting their direct role in regulating tumor angiogenesis and metastasis. In this review, we will focus on the signals mediated by this receptor trio via their shared ligands and their role in tumor growth and progression.

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“…In an animal model of lung cancer, blockage of CXCR7 by its antagonist CCX754 was observed to inhibit tumor growth, suggesting that CXCR7 possesses protumorigenic properties (49). Tumor endothelial cells (TECs) from renal cell carcinoma tissue were used in a previous study that hypothesized that the upregulation of CXCR7 in TECs is a result of tumor microenvironment factors, such as the levels of VEGF (50). Prior studies have indicated that CXCL14 is an inhibitor of the CXCL12-CXCR4 signaling axis, and is downregulated by DNA methylation in prostate (51) and lung cancer (52).…”

Section: Regulation Of CXC Chemokines In Angiogenesismentioning

confidence: 99%

Association between preeclampsia and the CXC chemokine family (Review)

Liu

Dai

Zhou

2015

Experimental and Therapeutic Medicine

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Abstract. Preeclampsia is a major cause of maternal and perinatal mortality and morbidity, characterized by gestational hypertension, proteinuria, systemic endothelial cell activation and an exaggerated inflammatory response. The precise cause of preeclampsia is not currently known; however, it is widely accepted that the pathogenesis of preeclampsia involves inadequate trophoblast invasion, leading to generalized endothelial dysfunction and an exaggerated inflammatory response. Chemokines are a superfamily of structurally similar proteins that mediate cell recruitment, angiogenesis, immunity and stem cell trafficking. CXC chemokines are a family of cytokines, unique in their ability to behave in a disparate manner in the regulation of angiogenesis. The CXC chemokine family further divides into two subfamilies; CXC ELR+, which promotes angiogenesis, and CXC ELR-, which inhibits angiogenesis. Furthermore, CXC chemokines are involved in the pathogenesis of various conditions, including malignant tumors, wound repair, chronic inflammation, atherosclerosis and potentially preeclampsia.

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CXCR7: A novel tumor endothelial marker in renal cell carcinoma

Cited by 66 publications

References 42 publications

CXCR7 and CXCR4 Expressions in Infiltrative Astrocytomas and Their Interactions with HIF1α Expression and IDH1 Mutation

CXCR7 and CXCR4 Expressions in Infiltrative Astrocytomas and Their Interactions with HIF1α Expression and IDH1 Mutation

Chemokine receptor trio: CXCR3, CXCR4 and CXCR7 crosstalk via CXCL11 and CXCL12

Association between preeclampsia and the CXC chemokine family (Review)

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