%0 Generic
%A D., Heckmann
%A S., Laufs
%A P., Maier
%A M., Zucknick
%A F.A., Giordano
%A M.R., Veldwijk
%A V., Eckstein
%A F., Wenz
%A W.J., Zeller
%A S., Fruehauf
%D 2011
%T Supplementary Material for: A Lentiviral CXCR4 Overexpression and Knockdown Model in Colorectal Cancer Cell Lines Reveals Plerixafor-Dependent Suppression of SDF-1α-Induced Migration and Invasion
%U https://karger.figshare.com/articles/dataset/Supplementary_Material_for_A_Lentiviral_CXCR4_Overexpression_and_Knockdown_Model_in_Colorectal_Cancer_Cell_Lines_Reveals_Plerixafor-Dependent_Suppression_of_SDF-1_-Induced_Migration_and_Invasion/5122906
%R 10.6084/m9.figshare.5122906.v1
%2 https://ndownloader.figshare.com/files/8708191
%K Chemokines
%K Invasion
%K Colorectal cancer
%K Plerixafor
%X Background: The development of distant metastasis is associated with poor outcome in patients with colorectal cancer (CRC). The stromal cell-derived factor-1 (SDF-1) and its receptor CXC chemokine receptor 4 (CXCR4) have pivotal roles in the chemotaxis of migrating tumor cells during metastasis. Thus, hampering the SDF-1/CXCR4 cross-talk is a promising strategy to suppress metastasis. Methods: We investigated the invasive behavior of the lentivirally CXCR4overexpressing CRC cell lines SW480, SW620 and RKO in chemotaxis and invasion assays toward an SDF-1α gradient. Low endogenous CXCR4 expression levels were determined by quantitative realtime polymerase chain reaction (PCR) and fluorescence-activated cell sorting (FACS) analyses. Results: A lentiviral CXCR4 overexpression and knockdown model was established in these CRC cells. In transwell migration assays, CXCR4 overexpression favored chemotaxis and invasion of cells in all 3 lines depending on an SDF-1α gradient (p < 0.001 vs. untransduced cells). Functional CXCR4 knockdown using lentiviral short hairpin RNA (shRNA) vectors significantly decreased the migration behavior in CRC cell lines (p < 0.001), confirming a CXCR4-specific effect. Pharmacologic inhibition of the SDF-1α/CXCR4 interaction by the bicyclam PlerixaforTM at 100 µM significantly abrogated CXCR4-dependent migration and invasion through MatrigelTM (SW480, SW620, RKO; p < 0.05). Conclusion: Our results indicate that a CXCR4-antagonistic therapy might prevent tumor cell dissemination and metastasis in CRC patients, consequently improving survival.
%I Karger Publishers