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Downregulation of the CXCR4 receptor inhibits cervical carcinoma metastatic behavior in vitro and in vivo
Author(s) -
Małgorzata Sekuła,
Katarzyna Miękus,
Marcin Majka
Publication year - 2014
Publication title -
international journal of oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.405
H-Index - 122
ISSN - 1019-6439
DOI - 10.3892/ijo.2014.2383
Subject(s) - downregulation and upregulation , cxcr4 , biology , in vivo , oncogene , cancer research , gene silencing , cell cycle , cell growth , receptor , apoptosis , chemokine , biochemistry , genetics , microbiology and biotechnology , gene
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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