Downregulation of the CXCR4 receptor inhibits cervical carcinoma metastatic behavior in vitro and in vivo

Int J Oncol. 2014 Jun;44(6):1853-60. doi: 10.3892/ijo.2014.2383. Epub 2014 Apr 11.

Abstract

Cervical carcinoma is frequently diagnosed among women, particularly in low and middle income countries. In this study, we investigated the role of the SDF-1/CXCR4 axis during cervical carcinoma growth and progression in vitro and in vivo. Downregulation of CXCR4 receptor using an RNA interference system led to almost complete inhibition of the receptor expression, activation and function. CXCR4 receptor silencing led to decreased ability to signal, to induce migration and to form holoclone-like colonies, with no influence on viability/proliferation of the cells. CXCR4-deficient cells had also significantly lower levels of MMP-9. Interestingly, downregulation of CXCR4 expression resulted in reduced tumor growth in vivo. Tumors generated by CXCR4-deficient cells had also lower expression of the proliferation marker Ki‑67 and decreased ability to engraft into lungs and spleen. Taken together, our results indicate that CXCR4 receptor may play an important role during cervical carcinoma invasion. In our study CXCR4 influenced invasive properties of cervical carcinoma cells both in vitro and in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma / genetics
  • Carcinoma / pathology*
  • Cell Proliferation / genetics
  • Down-Regulation
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Humans
  • Lung / pathology
  • Male
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Mice, SCID
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology*
  • Neoplasm Metastasis / pathology
  • Neoplasms, Experimental
  • Receptors, CXCR4 / genetics
  • Receptors, CXCR4 / metabolism*
  • Spleen / pathology
  • Uterine Cervical Neoplasms / pathology*

Substances

  • CXCR4 protein, human
  • Receptors, CXCR4
  • Matrix Metalloproteinase 9