SIVmac239-Nef Down-regulates Cell Surface Expression of CXCR4 in Tumor Cells and Inhibits Proliferation, Migration and Angiogenesis

• Published in: Anticancer research Vol. 32; no. 7; pp. 2759 - 2768
• Main Authors: CAI, Chengzhong, RODEPETER, Fiona R, ROSSMANN, Annette, TEYMOORTASH, Afshin, LEE, Jin-Seok, QUINT, Karl, DI FAZIO, Pietro, OCKER, Matthias, WERNER, Jochen A, MANDIC, Robert
• Format: Journal Article
• Language: English
• Published: Attiki International Institute of Anticancer Research 01.07.2012
• Subjects: Animals; Biological and medical sciences; Cell Growth Processes - physiology; Cell Movement - physiology; Cercopithecus aethiops; COS Cells; Down-Regulation; Gene Expression Regulation, Neoplastic; Gene Products, nef - genetics; Gene Products, nef - metabolism; HeLa Cells; Humans; Medical sciences; Neovascularization, Pathologic - genetics; Neovascularization, Pathologic - metabolism; Neovascularization, Pathologic - pathology; Receptors, CXCR4 - biosynthesis; Receptors, CXCR4 - genetics; Simian Immunodeficiency Virus - genetics; Simian Immunodeficiency Virus - metabolism; Transfection; Tumors; Cell proliferation; SIV; CXCR4; Chemokine receptor; Cell surface; HeLa; Angiogenesis; Cancerology; SDF-1α; Neovascularization; CXC chemokine; Tumor cell; CXCR4 chemokine receptor; Biological receptor; Malignant tumor; Hela cell line; Nef; Cell motility; cells; migration; Inhibitor; COS-7 cells; Stromal derived factor 1α; Cell migration; Cancer
• ISSN: 0250-7005; 1791-7530

To evaluate if the lentiviral accessory protein Nef can down-regulate the C-X-C chemokine receptor type 4 (CXCR4) in tumor cells and affect tumor cell proliferation, migration and angiogenesis. HeLa-(ACC) cells, which according to genotype analysis are virtually identical to the cervical cancer-derived HeLa cell line, were transfected with Nef from SIV(mac239) and expression levels of cell surface CXCR4 were monitored by flow cytometry. Real-time proliferation and migration of cells was measured with the xCELLigence system or with the in vitro scratch assay. In vitro tube formation was deployed to assess the effect of Nef on angiogenesis. Cell surface down-regulation of CXCR4 was observed in HeLa-(ACC) cells after Nef transfection, as well as in the monkey kidney-derived COS-7 cell line after co-transfection of CXCR4 and Nef. Proliferation, as well as migration, of Nef-transfected HeLa-(ACC) cells appeared to be significantly reduced. In vitro tube formation was markedly lowered after Nef transfection, and CXCR4 knockdown with siRNA. SIV-Nef could serve as an interesting tool to study the biological behavior of CXCR4-expressing tumor cells and could be helpful in the discovery of new therapeutic approaches for the treatment of CXCR4-positive tumors.