Nef from SIVmac239 down-modulates cell surface CXCR4 in tumor cells and inhibits proliferation, migration and angiogenesis

Aim: To evaluate if the lentiviral accessory protein Nef can down-regulate CXCR4 in tumor cells and affect tumor cell proliferation, migration and angiogenesis. Materials and Methods: HeLa-ACC cells were transfected with Nef from SIVmac239 and expression levels of cell surface CXCR4 were monitored b...

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1. Verfasser: Cai, Chengzhong
Beteiligte: Mandic, Robert (Prof. Dr.) (BetreuerIn (Doktorarbeit))
Format: Dissertation
Sprache:Englisch
Veröffentlicht: Philipps-Universität Marburg 2012
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Zusammenfassung:Aim: To evaluate if the lentiviral accessory protein Nef can down-regulate CXCR4 in tumor cells and affect tumor cell proliferation, migration and angiogenesis. Materials and Methods: HeLa-ACC cells were transfected with Nef from SIVmac239 and expression levels of cell surface CXCR4 were monitored by FACS analysis. Real-time proliferation and migration of cells was measured with the xCELLigence system or in vitro scratch assay. In vitro tube formation was deployed to assess the effect of Nef on angiogenesis. Results: Cell surface down-modulation of CXCR4 could be observed in HeLa-ACC cells after Nef-transfection as well as in COS-7 cells after co-transfection of CXCR4 and Nef. Proliferation as well as migration of Nef-transfected HeLa-ACC cells appeared significantly reduced. In vitro tube formation was markedly lowered after Nef-transfection or CXCR4 knockdown with siRNA. Conclusion: SIV-Nef could serve as an interesting tool to study the biologic behavior of CXCR4-expressing tumor cells and could be helpful in the discovery of new therapeutic approaches for the treatment of CXCR4-positive tumors.
Umfang:84 Seiten
DOI:10.17192/z2011.0877