title: Downregulation of the CXCR4 receptor inhibits cervical carcinoma metastatic behavior in vitro and in vivo.
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.
authors.affiliation: Department of Transplantation, Polish-American Institute of Pediatrics, Jagiellonian University, 30-663 Cracow, Poland.
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Sekuła
authors.affiliation: Department of General Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, 30-663 Cracow, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Miekus
authors.affiliation: Department of Transplantation, Polish-American Institute of Pediatrics, Jagiellonian University, 30-663 Cracow, Poland.
authors.forename: Marcin
authors.initials: M
authors.lastname: Majka
mesh_terms: D000818:Animals; D002277:Carcinoma / Q000235:genetics / Q000473:pathology*; D049109:Cell Proliferation / Q000235:genetics; D015536:Down-Regulation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008168:Lung / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D016513:Mice, SCID; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology*; D009362:Neoplasm Metastasis / Q000473:pathology; D009374:Neoplasms, Experimental; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism*; D013154:Spleen / Q000473:pathology; D002583:Uterine Cervical Neoplasms / Q000473:pathology*
chemical_list: C527276:CXCR4 protein, human; D019718:Receptors, CXCR4; D020780:Matrix Metalloproteinase 9
references.citation: J Mol Histol. 2004 Mar;35(3):233-45
references.pmid: 15339043
references.citation: Cancer Res. 2005 Aug 1;65(15):6543-50
references.pmid: 16061633
references.citation: Cancer Cell. 2004 Jul;6(1):17-32
references.pmid: 15261139
references.citation: Int J Cancer. 2006 Nov 1;119(9):2026-9
references.pmid: 16671092
references.citation: Cancer Lett. 2007 Oct 28;256(2):137-65
references.pmid: 17629396
references.citation: Breast Cancer Res. 2003;5(5):R144-50
references.pmid: 12927045
references.citation: Biochem Biophys Res Commun. 2007 Aug 3;359(3):716-22
references.pmid: 17559806
references.citation: Genes Dev. 2001 Mar 1;15(5):485-90
references.pmid: 11238371
references.citation: Stem Cells. 2005 Aug;23(7):879-94
references.pmid: 15888687
references.citation: Pharmacol Ther. 2013 May;138(2):285-93
references.pmid: 23384596
references.citation: Cancer Res. 2005 Feb 1;65(3):967-71
references.pmid: 15705897
references.citation: Cancer Res. 2008 Mar 15;68(6):1820-5
references.pmid: 18339862
references.citation: Thromb Haemost. 2007 May;97(5):714-21
references.pmid: 17479181
references.citation: Cancer Res. 2004 May 15;64(10):3500-7
references.pmid: 15150104
references.citation: J Pathol. 2001 Jan;193(1):48-54
references.pmid: 11169515
references.citation: Br J Cancer. 2004 Dec 13;91(12):2018-25
references.pmid: 15545971
references.citation: J Natl Cancer Inst. 2011 Mar 2;103(5):368-83
references.pmid: 21282563
references.citation: Clin Transl Oncol. 2007 Jun;9(6):347-54
references.pmid: 17594948
references.citation: J Biol Chem. 2003 Jun 13;278(24):21631-8
references.pmid: 12690099
references.citation: Gynecol Oncol. 1999 Jun;73(3):372-82
references.pmid: 10366463
references.citation: Clin Cancer Res. 2010 Jun 15;16(12):3121-9
references.pmid: 20530700
references.citation: Cancer Res. 2003 Oct 1;63(19):6537-42
references.pmid: 14559848
references.citation: Cell. 2005 May 6;121(3):335-48
references.pmid: 15882617
references.citation: Cancer Res. 2004 Dec 1;64(23):8604-12
references.pmid: 15574767
references.citation: Ann Oncol. 2007 Jan;18(1):70-76
references.pmid: 17032700
references.citation: Folia Histochem Cytobiol. 2006;44(3):155-64
references.pmid: 16977794
references.citation: Immunity. 2003 Aug;19(2):257-67
references.pmid: 12932359
references.citation: Immunity. 2000 Feb;12(2):121-7
references.pmid: 10714678
references.citation: Cancer Res. 2002 Mar 15;62(6):1832-7
references.pmid: 11912162
references.citation: Cell Death Dis. 2013 Jan 17;4:e459
references.pmid: 23328666
references.citation: BMC Cancer. 2011 Nov 14;11:486
references.pmid: 22081974
references.citation: Hippokratia. 2006 Jul;10(3):112-5
references.pmid: 20351805
references.citation: Curr Cancer Drug Targets. 2013 Feb;13(2):143-56
references.pmid: 23297827
references.citation: Proc Natl Acad Sci U S A. 1987 Apr;84(8):2302-6
references.pmid: 2436229
references.citation: Stem Cells. 2003;21(4):481-94
references.pmid: 12832701
references.citation: Clin Cancer Res. 2010 Jun 1;16(11):2927-31
references.pmid: 20484021
references.citation: Nature. 2001 Mar 1;410(6824):50-6
references.pmid: 11242036
references.citation: Cancer Res. 2005 Oct 1;65(19):8944-50
references.pmid: 16204067