| Online-Ressource |
Verfasst von: | Heckmann, Doreen [VerfasserIn]  |
| Maier-Laufs, Stephanie [VerfasserIn]  |
| Maier, Patrick [VerfasserIn]  |
| Zucknick, Manuela [VerfasserIn]  |
| Giordano, Frank Anton [VerfasserIn]  |
| Veldwijk, Marlon Romano [VerfasserIn]  |
| Eckstein, Volker [VerfasserIn]  |
| Wenz, Frederik [VerfasserIn]  |
| Zeller, W. Jens [VerfasserIn]  |
| Frühauf, Stefan [VerfasserIn]  |
| Allgayer, Heike [VerfasserIn]  |
Titel: | A lentiviral CXCR4 overexpression and knockdown model in colorectal cancer cell lines reveals plerixafor-dependent suppression of SDF-1α-induced migration and invasion |
Verf.angabe: | Doreen Heckmann, Stephanie Laufs, Patrick Maier, Manuela Zucknick, Frank A. Giordano, Marlon R. Veldwijk, Volker Eckstein, Frederik Wenz, W. Jens Zeller, Stefan Fruehauf, Heike Allgayer |
E-Jahr: | 2011 |
Jahr: | [October 2011] |
Umfang: | 7 S. |
Illustrationen: | Diagramme |
Fussnoten: | Gesehen am 28.09.2022 |
Schrift/Sprache: | Zusammenfassung in deutscher Sprache |
Titel Quelle: | Enthalten in: Onkologie |
Ort Quelle: | Basel : Karger, 1978 |
Jahr Quelle: | 2011 |
Band/Heft Quelle: | 34(2011), 10, Seite 502-508 |
ISSN Quelle: | 1423-0240 |
Abstract: | 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 Plerixafor<sup>TM</sup> at 100 µM significantly abrogated CXCR4-dependent migration and invasion through Matrigel<sup>TM</sup> (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. |
DOI: | doi:10.1159/000332390 |
URL: | Bitte beachten Sie: Dies ist ein Bibliographieeintrag. Ein Volltextzugriff für Mitglieder der Universität besteht hier nur, falls für die entsprechende Zeitschrift/den entsprechenden Sammelband ein Abonnement besteht oder es sich um einen OpenAccess-Titel handelt.
Volltext: https://doi.org/10.1159/000332390 |
| Volltext: https://www.karger.com/Article/FullText/332390 |
| DOI: https://doi.org/10.1159/000332390 |
Datenträger: | Online-Ressource |
Sprache: | eng |
K10plus-PPN: | 1817710931 |
Verknüpfungen: | → Zeitschrift |
¬A¬ lentiviral CXCR4 overexpression and knockdown model in colorectal cancer cell lines reveals plerixafor-dependent suppression of SDF-1α-induced migration and invasion / Heckmann, Doreen [VerfasserIn]; [October 2011] (Online-Ressource)