Role of CXCR7 and Effects on CXCL12 in SiHa Cells and Upregulation in Cervical Squamous Cell Carcinomas in Uighur Women

  • Published : 2014.11.28


CXCR7 is involved in tumor development and metastasis in multiple malignancies. However, the function and molecular mechanisms of action of CXCR7 in human cervical cancer are still unclear. In the present study a loss of-function approach was used to observe the effects of recombinant CXCR7 specific small interfering RNA pBSilence1.1 plasmids on biological behavior including proliferative activity and invasive potential, as indicated by MTT assays with the cervical cancer SiHa cell line in vitro. Reverse transcription polymerase chain reaction and Western blotting revealed that CXCR7 was downregulated in transfected compared with control cells, associated with inhibited cell growth, invasiveness and migration. The expression of CXCR7 and CXCL12 was also determined immunohistochemically in 152 paraffin-embedded, cervical squamous cell carcinoma (CSCC) and cervical intraepithelial neoplasia (CIN), or normal cervical epithelial to assess clinico-pathological pattern and CXCR7 status with respect to cell differentiation and lymph node metastasis in Uighur patients with CSCC. CXCR7 and CXCL12 expression was higher in cervical cancer than CIN and normal cervical mucosa, especially in those with higher stage and lymph node metastasis. CXCL12 appeared to be positively regulated by CXCR7 at the post-transcriptional level in CSCC. We propose that aberrant expression of CXCR7 plays a role in carcinogenesis, differentiation and metastasis of CSCC, implying its use as a potential target for clinical biomarkers in differentiation and lymph node metastasis.


Supported by : Xinjiang medical university


  1. Balkwill F (2004). Cancer and the chemokine network. Nat Rev Cancer, 4, 540-50.
  2. Cai C, Rodepeter FR, Rossmann A, et al (2012). SIVmac239-Nef down-regulates cell surface expression of CXCR4 in tumor cells and inhibits proliferation, migration and angiogenesis. Anticancer Res, 32, 2759-68.
  3. Heinrich EL, Lee W, Lu J, Lowy AM, Kim J (2012). Chemokine CXCL12 activates dual CXCR4 and CXCR7-mediated signaling pathways in pancreatic cancer cells. J Transl Med, 10, 68.
  4. Huang Y, Zhang J, Cui ZM, Zhao J, Zheng Y (2013). Expression of the CXCL12/CXCR4 and CXCL16/CXCR6 axes in cervical intraepithelial neoplasia and cervical cancer. Chin J Cancer, 32, 289-96.
  5. Kodama J, Hasengaowa, Kusumoto T, et al (2007). Association of CXCR4 and CCR7 chemokine receptor expression and lymph node metastasis in human cervical cancer. Ann Oncol, 18, 70-6.
  6. Ma D, Ling X (2001). Advances in the epidemiology and etiology of cervical cancer. J Practical Obstet Gynecol, 17, 61-3.
  7. Miao Z, Luker KE, Summers BC, et al (2007). CXCR7 (RDC1) promotes breast and lung tumor growth in vivo and is expressed on tumor-associated vasculature. Proc Natl Acad Sci USA, 4, 5735-40.
  8. Paradkar PH, Joshi JV, Mertia PN, Agashe SV, Vaidya RA (2014). Role of cytokines in genesis, progression and prognosis of cervical cancer. Asian Pac J Cancer Prev, 15, 3851-64.
  9. Roy I, Zimmerman NP, Mackinnon AC, et al (2014). CXCL12 chemokine expression suppresses human pancreatic cancer growth and metastasis. Plops One, 9, 90400.
  10. Schrevel M, Karim R, Ter Haar NT, et al (2012). CXCR7 expression is associated with disease-free and disease-specific survival in cervical cancer patients. Br J Cancer, 106, 1520-5.
  11. Shen B, Zheng MQ, Lu JW, et al (2013). CXCL12-CXCR4 promotes proliferation and invasion of pancreatic cancer cells. Asian Pac J Cancer Prev, 14, 5403-8.
  12. Sun X, Cheng G, Hao M, Zheng J, et al (2010). CXCL12/ CXCR4/ CXCR7 chemokine axis and cancer progression. Cancer Metastasis Rev, 29, 709-22.
  13. Suzuk L, Peng YH, Zhou FS (2006). Analysis of the cervical cancer distribution in Xinjiang. J Xinjiang Med Univ, 29, 569-71.
  14. Tachezy M, Zander h, Gebauer F, et al (2013). CXCR7 expression in esophageal cancer. J Transl Med, 11, 238.
  15. Wani N, Nasser MW, Ahirwar DK, et al (2014). C-X-C motif chemokine 12/C-X-C chemokine receptor type 7 signaling regulates breast cancer growth and metastasis by modulating the tumor microenvironment. Breast Cancer Res, 16, 54.
  16. Wen WW, Xie S, Xin XL, et al (2013). Oligomannurarate sulfate inhibits CXCL12/SDF-1-mediated proliferation and invasion of human tumor cells in vitro. Acta Pharmacol Sin, 34, 1554-9.
  17. Xue TC, Chen RX, Ren ZG, et al ( 2013). Transmembrane receptor CXCR7 increases the risk of extrahepatic metastasis of relatively well-differentiated hepatocellular carcinoma through upregulation of osteopontin. Oncol Rep, 30, 105-10.
  18. Zabel BA, Lewen S, Berahovich RD, Jaen JC, Schall TJ (2011). The novel chemokine receptor CXCR7 regulates transendothelial migration of cancer cells. Mol Cancer, 10, 73.
  19. Zhang GQ, Liu KJ, Lai XJ, et al (2003). The distribution of Malignant tumor in the Affiliated Tumor Hospital of Xinjiang Medical University from 1989 to 2002. J Xinjiang Med Univ, 26, 393-5.

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