| A Lentiviral CXCR4 Overexpression and Knockdown Model in Colorectal Cancer Cell Lines Reveals Plerixafor-Dependent Suppression of SDF-1α-Induced Migration and Invasion. | |
| | |
MedLine Citation:
|
PMID: 21985848 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
|
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(TM) at 100 μM significantly abrogated CXCR4-dependent migration and invasion through Matrigel(TM) (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. |
| | |
Authors:
|
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 |
Related Documents
:
|
22236188 - Differential expression and function of peroxiredoxin 1 and peroxiredoxin 6 in cancerou... 22227008 - The flavonoid eupatorin inactivates the mitotic checkpoint leading to polyploidy and ap... 22043808 - Cell colony formation induced by xenopus egg extract as a marker for improvement of clo... 22266188 - Secreted 70 kilodalton lumican stimulates growth and inhibits invasion of human pancrea... 15885728 - Morphologic changes in alveolar macrophages in response to uvec-activated pulmonary typ... 9294398 - Long-term enhanced chromaffin cell survival and behavioral recovery in hemiparkinsonian... |
Publication Detail:
|
Type: Journal Article Date: 2011-09-20 |
Journal Detail:
|
Title: Onkologie Volume: 34 ISSN: 1423-0240 ISO Abbreviation: Onkologie Publication Date: 2011 |
Date Detail:
|
Created Date: 2011-10-11 Completed Date: - Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 7808556 Medline TA: Onkologie Country: Switzerland |
Other Details:
|
Languages: eng Pagination: 502-8 Citation Subset: IM |
Copyright Information:
|
Copyright © 2011 S. Karger AG, Basel. |
Affiliation:
|
Molecular Oncology of Solid Tumors, DKFZ (German Cancer Research Center), Heidelberg, Germany. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Diagnostic Value of the Serum-Specific IgE Ratio of ?-5 Gliadin to Wheat in Adult Patients with Whea...
Next Document: Management of stage I testicular seminoma over a period of 49 years.