High expression of CXCR4, CXCR7 and SDF-1 predicts poor survival in renal cell carcinoma

Wang, Linhui; Chen, Wei; Gao, Li; Yang, Qing; Liu, Bing; Wu, Zhenjie; Wang, Yang; Sun, Ying-hao

doi:10.1186/1477-7819-10-212

Cited by 58 publications

(52 citation statements)

References 26 publications

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“…The results were consistent with those of other studies indicating that both RCC cell lines and human RCC specimens exhibit elevated expressions of CXCR4, but not CXCL12, compared with normal kidney specimens. 34,35 The strong expression of CXCR4 in RCC is associated with metastasis and is predictive of worse prognosis. 36,37 The results here further show that patients with metastatic RCC have higher CXCR4 and Gal-1 coexpression than those with primary tumors (data not shown).…”

Section: Discussionmentioning

confidence: 99%

Galectin-1 Upregulates CXCR4 to Promote Tumor Progression and Poor Outcome in Kidney Cancer

Huang

Tang

Chung

et al. 2014

Journal of the American Society of Nephrology

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Galectin-1, a b-galactoside-binding lectin, is involved in many physiologic and pathologic processes, including cell adhesion, differentiation, angiogenesis, and tumor progression. However, the role of galectin-1 in kidney cancer remains elusive. This study evaluated the role of galectin-1 in the progression and clinical prognosis of renal cell carcinoma. We found significant overexpression of galectin-1 in both kidney cancer cell lines and metastatic tissue specimens from patients with renal cell carcinoma. Knockdown of galectin-1 gene expression in renal cancer cell lines reduced cell invasion, clonogenic ability, and epithelial-mesenchymal transition in vitro; reduced tumor outgrowth in vivo; and inhibited the angiogenesis-inducing activity of these cells in vitro and in vivo. Galectin-1 knockdown decreased CXCR4 expression levels in kidney cancer cells, and restoration of CXCR4 expression in galectin-1-silenced cells rescued cell motility and clonogenic ability. Additional studies suggested that galectin-1 induced CXCR4 expression through activation of nuclear factor-kB (NF-kB). Analysis of patient specimens confirmed the clinical significance and positive correlation between galectin-1 and CXCR4 expression levels and revealed concomitant overexpression of galectin-1 and CXCR4 associated adversely with overall and disease-free survival. Our findings suggest that galectin-1 promotes tumor progression through upregulation of CXCR4 via NF-kB. The coordinated upregulation of galectin-1 and CXCR4 may be a novel prognostic factor for survival in patients with renal cell carcinoma and the galectin-1-CXCR4 axis may serve as a therapeutic target in this disease. 25: 148625: -149525: , 201425: . doi: 10.1681 Renal cell carcinoma (RCC) accounts for approximately 4% of all adult malignancies. 1 More than one third of patients will present with locally advanced or metastatic disease at the time of diagnosis. 2 The 5-year survival rate of metastatic RCC is only 10% because of resistance to chemotherapy and radiation therapy. 3 Although cytokine therapy with IFN-a and IL-2 is the gold standard treatment, its overall efficacy rate is limited by its significant toxicity. 4 Recently, several molecular targeting drugs, including sunitinib and temsirolimus, have been approved for advanced RCC. 4 However, treatment response is not long-standing and overall survival remains poor. Thus, the identification of novel molecular targets in RCC is urgently needed for the development of effective therapies. J Am Soc Nephrol

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Section: Discussionmentioning

confidence: 99%

Galectin-1 Upregulates CXCR4 to Promote Tumor Progression and Poor Outcome in Kidney Cancer

Huang

Tang

Chung

et al. 2014

Journal of the American Society of Nephrology

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“…This study was initiated from the aspect of CXCR7 expression, and its correlation with tumor grade, tumor stage, and lymph node metastasis. In cervical cancer research [30], colorectal cancer research by Xu et al [19] cutaneous squamous cell carcinoma research by Hu et al [21] renal cancer research by Wang et al [26] and gallbladder cancer research by Yao et al [27] all of these studies have consistent results for tumor grade, stage and lymph node metastasis [30][31][32][33][34]. These significant clinicopathological relative factors revealed their roles in tumor development [35][36][37][38][39][40].…”

Section: Discussionmentioning

confidence: 98%

“…Shen et al regarded CXCR4 as a key receptor involved in tumor invasion and prognosis, while Liu et al [9] considered CXCR7 to be more important for long term survival in pancreatic cancer patients [9,23,24]. Implications of CXCR7 have been revealed in various tumors, including nervous system, digestive system, endocrine system, genital system, blood system, respiratory system, and urinary system, respectively [9,15,[25][26][27][28][29]. However, systemic study of the correlation of CXCR7 with clinicopathogy and prognosis in various tumors is still vacant.…”

Section: Discussionmentioning

confidence: 99%

Meta-analysis of CXCR7 Expression Related to Clinical Prognosis in Cancers

Qing¹,

Wen²

2016

J Integr Oncol

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Purpose: Recently, higher expression of chemokine receptors in patients with various cancer types has been observed and indicated to have prognostic significance in the clinical progression of cancers. Former research has determined that CXCR7, as a member of chemokine receptor C-X-C family, empowers greater affinity with chemokine CXCL12 than CXCR4. The present study investigated the correlation of clinical characteristics and CXCR7 expression in cancers using meta-analysis. Methods:A comprehensive search on Pubmed and Web of Science identified CXCR7-related clinical studies. Methodological quality of these studies was evaluated and all the data were extracted, calculated and analyzed. This meta-analysis was carried out with Stata 12.0. Results:Fifteen eligible studies consisting of 1780 participants were included. The results showed that CXCR7 significantly relates to tumor occurrence (pooled RR=3.12, 95% CI: 1.71-5.70, P=0.000), tumor grades (pooled RR=1.41, 95% CI: 1.14-1.75, P=0.002), tumor stages (pooled RR=1.51, 95% CI: 1.26-1.82, P=0.000) and lymph node metastasis (pooled RR=1.49, 95% CI: 1.14-1.94, P=0.000), respectively. Conclusion:Highly expressed chemokine receptor CXCR7 potentially increases tumor occurrence risk. Higher CXCR7 expression is associated with poorer prognosis, advanced stages, differentiation grades and poor lymph node metastasis in patients with various cancers. Thus, highly expressed CXCR7 could be a potential biomarker in the prognosis of cancers.

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“…CXCR7 was found to be differentially expressed in pancreatic cancer, while knockdown of CXCR7 resulted in decreased migration and invasion (18). The expression of CXCR7 was found to be upregulated in renal cell (10) and human hepatocellular carcinoma (19), and human brain tumors (20). Overexpression of CXCR7 was found to be associated with metastasis and poor survival of patients with hepatocellular carcinoma, indicating its potential function as a therapeutic target (21).…”

Section: Discussionmentioning

confidence: 99%

“…CXC chemokine receptor 7 (CXCR7), as the receptor for CXCL12 with higher binding affinity, is overexpressed in glioma and regulates tumor proliferation via the ERK and AKT pathways (6,7). Based on the cellular localization, positive expression of CXCR7, mainly detected in the cytoplasm, mediates anti-apoptotic effects in glioma cells and indicates a poor prognosis in gallbladder cancer (8,9) and renal cell carcinoma (10). These data suggest that CXCR7 is a promising therapeutic target.…”

Section: Introductionmentioning

confidence: 97%

Knockdown of CXCR7 inhibits proliferation and invasion of osteosarcoma cells through inhibition of the PI3K/Akt and β-arrestin pathways

et al. 2014

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Abstract. CXC chemokine receptor 7 (CXCR7) has been implicated in tumor development and metastasis in multiple malignancies. Yet, the function and molecular mechanisms of CXCR7 in human osteosarcoma (OS) are still unclear. The aim of the present study was to investigate the role of CXCR7 in human OS. The expression of CXCR7 was assessed by immunohistochemical assay using a tissue microarray procedure in 45 cases of OS tissues. A loss-of-function approach was used to observe the effects of lentiviral vector-mediated CXCR7 siRNA (Lv-siCXCR7) on biological behaviors including proliferative activities and invasive potential, as indicated by MTT and Transwell assays in OS (MG-63 and U-2 OS) cells. The results showed that the expression of CXCR7 protein in OS tissues was significantly increased compared to that in adjacent non-cancerous tissues (68.9 vs. 53.3%, P=0.033), and was correlated with the distant metastasis of the tumors (P=0.004). Knockdown of CXCR7 suppressed proliferation and invasion of OS cells through decreased expression of PI3K, AKT, β-arrestin, proliferating cell nuclear antigen (PCNA), and matrix metalloproteinase-9 (MMP-9). In addition, the tumor volume in U-2 OS subcutaneous tumor models treated with Lv-siCXCR7 was significantly smaller than the tumor volume in the negative control group (P<0.01). Collectively, our findings indicate that upregulation of CXCR7 expression is correlated with distant metastasis of OS, while knockdown of CXCR7 blocks the development of OS cells through inhibition of the PI3K/AKT and β-arrestin pathways, suggesting that CXCR7 may serve as a potential therapeutic target for the treatment of cancer.

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High expression of CXCR4, CXCR7 and SDF-1 predicts poor survival in renal cell carcinoma

Cited by 58 publications

References 26 publications

Galectin-1 Upregulates CXCR4 to Promote Tumor Progression and Poor Outcome in Kidney Cancer

Galectin-1 Upregulates CXCR4 to Promote Tumor Progression and Poor Outcome in Kidney Cancer

Meta-analysis of CXCR7 Expression Related to Clinical Prognosis in Cancers

Knockdown of CXCR7 inhibits proliferation and invasion of osteosarcoma cells through inhibition of the PI3K/Akt and β-arrestin pathways

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