Chemokine receptor CXCR7 regulates the invasion, angiogenesis and tumor growth of human hepatocellular carcinoma cells

Ke Zheng; Hong-Yuan Li; Xin-Liang Su; Xiao-Yi Wang; Tian Tian; Fan Li; Guo-Sheng Ren
January 2010
Journal of Experimental & Clinical Cancer Research (17569966);2010, Vol. 29, p31
Academic Journal
Background: In spite of recent advances in diagnostic and therapeutic measures, the prognosis of hepatocellular carcinoma (HCC) patients remains poor. Therefore, it is crucial to understand what factors are involved in promoting development of HCC. Evidence is accumulating that members of the chemokine receptor family are viewed as promising therapeutic targets in the fight against cancer. More recent studies have revealed that chemokine receptor CXCR7 plays an important role in cancer development. However, little is known about the effect of CXCR7 on the process of HCC cell invasion and angiogenesis. The aim of this study is to investigate the expression of CXCR7 in hepatocellular carcinoma tissues and cell lines and to evaluate the role of CXCR7 in tumor growth, angiogenesis and invasion of HCC cells. Methods: We constructed CXCR7 expressing shRNA, and CXCR7shRNA was subsequently stably transfected into human HCC cells. We evaluated the effect of CXCR7 inhibition on cell invasion, adhesion, VEGF secretion, tube formation and tumor growth. Immunohistochemistry was done to assess the expression of CXCR7 in human hepatocellular carcinoma tissues and CD31 in tumor of mice. We also evaluated the effect of VEGF stimulation on expression of CXCR7. Results: CXCR7 was overexpressed in hepatocellular carcinoma tissues. We showed that high invasive potential HCC cell lines express high levels of CXCR7. In vitro, CXCL12 was found to induce invasion, adhesion, tube formation, and VEGF secretion in SMMC-7721 cells. These biological effects were inhibited by silencing of CXCR7 in SMMC-7721 cells. In addition, we also found that VEGF stimulation can up-regulate CXCR7 expression in SMMC- 7721 cells and HUVECs. More importantly, enhanced expression of CXCR7 by VEGF was founctional. In vivo, tumor growth and angiogenesis were suppressed by knockdown of CXCR7 in SMMC-7721 cells. However, silencing of CXCR7 did not affect metastasis of tumor in vivo. Conclusions: Increased CXCR7 expression was found in hepatocellular carcinoma tissues. Knockdown of CXCR7 expression by transfected with CXCR7shRNA significantly inhibits SMMC-7721 cells invasion, adhesion and angiogenesis. Finally, down-regulation of CXCR7 expression lead to a reduction of tumor growth in a xenograft model of HCC. This study provides new insights into the significance of CXCR7 in invasion and angiogenesis of HCC.


Related Articles

  • Vascular remodeling in cancer. Farnsworth, R H; Lackmann, M; Achen, M G; Stacker, S A // Oncogene;7/3/2014, Vol. 33 Issue 27, p3496 

    The growth and dissemination of tumors rely on an altered vascular network, which supports their survival and expansion and provides accessibility to the vasculature and a route of transport for metastasizing tumor cells. The remodeling of vascular structures through generation of new vessels...

  • Mysteries of TGF-β paradox in benign and malignant cells. Qiang Zhang; NengwangYu; Chung Lee // Frontiers in Oncology;May2014, Vol. 4, p1 

    TGF-β regulates a wide range of biological functions including embryonic development, wound healing, organogenesis, immune modulation, and cancer progression. Interestingly, TGF-β is known to inhibit cell growth in benign cells but promote progression in cancer cells; this phenomenon is...

  • CK2 Inhibitor CX-4945 Blocks TGF-β1-Induced Epithelial-to-Mesenchymal Transition in A549 Human Lung Adenocarcinoma Cells. Kim, Jiyeon; Hwan Kim, Seong // PLoS ONE;Sep2013, Vol. 8 Issue 9, p1 

    Background:The epithelial-to-mesenchymal transition (EMT) is a major phenotype of cancer metastasis and invasion. As a druggable cancer target, the inhibition of protein kinase CK2 (formally named to casein kinase 2) has been suggested as a promising therapeutic strategy to treat EMT-controlled...

  • Role of TGF-β signaling in curcumin-mediated inhibition of tumorigenicity of human lung cancer cells. Datta, Raktima; Halder, Sunil; Zhang, Binhao // Journal of Cancer Research & Clinical Oncology;Apr2013, Vol. 139 Issue 4, p563 

    Purpose: Curcumin has been shown to have potent anticancer activities like inhibition of cell proliferation, induction of apoptosis, and suppression of angiogenesis. Transforming growth factor-β (TGF-β) signaling plays a complex role in tumor suppression and promotion depending on the...

  • Tumor Secretion of CCL22 Activates Intratumoral Treg Infiltration and Is Independent Prognostic Predictor of Breast Cancer. Li, Ya-Qing; Liu, Fang-Fang; Zhang, Xin-Min; Guo, Xiao-Jing; Ren, Mei-Jing; Fu, Li // PLoS ONE;Oct2013, Vol. 8 Issue 10, p1 

    It has been reported that dense intratumoral infiltration of Foxp3 +Tregs (Tregs) was an independent factor for poor prognosis of breast cancer (BC) patients. However, the cytokines activating the Treg infiltration are not known. This study was undertaken to evaluate the role of CCL22 and...

  • Tissue-specific differential antitumour effect of molecular forms of fractalkine in a mouse model of metastatic colon cancer. Vitale, S.; Cambien, B.; Karimdjee, B. F.; Barthel, R.; Staccini, P.; Luci, C.; Breittmayer, V.; Anjuère, F.; Schmicl-Alliana, A.; Schmid-Antomarchi, H. // Gut;Mar2007, Vol. 56 Issue 3, p365 

    Background and aims: Fractalkine, a chemokine that presents as both a secreted and a membrane-anchored form, has been described as having tumour-suppressive activities in standard subcutaneous models. Here, we investigate the antitumour effect of fractalkine, in its three molecular forms, in two...

  • Doxorubicin in Combination with a Small TGFβ Inhibitor: A Potential Novel Therapy for Metastatic Breast Cancer in Mouse Models. Bandyopadhyay, Abhik; Long Wang; Agyin, Joseph; Yuping Tang; Shu Lin; I-Tien Yeh; Keya De; Lu-Zhe Sun // PLoS ONE;2010, Vol. 5 Issue 4, p1 

    Background: Recent studies suggested that induction of epithelial-mesenchymal transition (EMT) might confer both metastatic and self-renewal properties to breast tumor cells resulting in drug resistance and tumor recurrence. TGFb is a potent inducer of EMT and has been shown to promote tumor...

  • High Expression of IGFBP7 in Fibroblasts Induced by Colorectal Cancer Cells Is Co-Regulated by TGF-β and Wnt Signaling in a Smad2/3-Dvl2/3-Dependent Manner. Rao, Cui; Lin, Shan-Li; Ruan, Wen-Jing; Wen, Huan; Wu, Dan-Ju; Deng, Hong // PLoS ONE;Jan2014, Vol. 9 Issue 1, p1 

    Fibroblasts in the tumor microenvironment are a key determinant in cancer progression and may be a promising target for cancer therapy. Insulin-like growth factor binding protein 7 (IGFBP7) is known as a tumor suppressor in colorectal cancer (CRC). The present study investigated the inductive...

  • miR-24-3p suppresses cellar proliferation in hepatocellular carcinoma. Jie Chen; Hong-Lin Luo; Fei-Xiang Wu; Jun-Jie Liu; Tao Luo; Xiao-Hui Fan; Tao Bai; Le-Qun Li // International Journal of Clinical & Experimental Medicine;2016, Vol. 9 Issue 11, p21672 

    Deregulation of microRNAs is a frequent event in the tumorigenesis and tumor progression. The aim of this study was to investigate the potential role of miR-24-3p expression in hepatocellular Carcinoma (HCC). The expression level of miR-24-3p was detected in HCC tissues and HCC cell lines...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics