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

Sekuła,Małgorzata; Miekus,Katarzyna; Majka,Marcin

doi:10.3892/ijo.2014.2383

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

Authors:
- Małgorzata Sekuła
- Katarzyna Miekus
- Marcin Majka
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Affiliations: Department of Transplantation, Polish-American Institute of Pediatrics, Jagiellonian University, 30-663 Cracow, Poland, Department of General Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-663 Cracow, Poland
Published online on: April 11, 2014 https://doi.org/10.3892/ijo.2014.2383
Pages: 1853-1860
Copyright: © Sekuła et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

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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.

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