Next Article in Journal
Photonic Therapy in Periodontal Diseases an Overview with Appraisal of the Literature and Reasoned Treatment Recommendations
Next Article in Special Issue
Immune and Inflammatory Cells of the Tumor Microenvironment Represent Novel Therapeutic Targets in Classical Hodgkin Lymphoma
Previous Article in Journal
Holothuria Leucospilota Polysaccharides Ameliorate Hyperlipidemia in High-Fat Diet-Induced Rats via Short-Chain Fatty Acids Production and Lipid Metabolism Regulation
Previous Article in Special Issue
Engaging Cytotoxic T and NK Cells for Immunotherapy in Chronic Lymphocytic Leukemia
Open AccessArticle

The CXCR4–CXCL12-Axis Is of Prognostic Relevance in DLBCL and Its Antagonists Exert Pro-Apoptotic Effects In Vitro

1
Division of Hematology, Medical University Graz; Auenbruggerplatz 38, 8036 Graz, Austria
2
Division of Cell Biology, Histology and Embryology, Gottfried Schatz Research Center for Cell Signaling, Metabolism and Aging, Medical University of Graz, Neue Stiftingtalstraße 6/II, 8010 Graz, Austria
3
Otto Loewi Research Center for Vascular Biology, Immunology and Inflammation, Division of Pharmacology, Medical University of Graz, Universitätsplatz 4/I, 8010 Graz, Austria
4
Division of General Otorhinolaryngology, Medical University of Graz, Auenbruggerplatz 26, 8036 Graz, Austria
5
Institute of Organic Chemistry, Graz University of Technology, Stremayrgasse 9/4, 8010 Graz, Austria
6
Diagnostic & Research Institute of Pathology, Medical University Graz, Neue Stiftingtalstraße 6, 8010 Graz, Austria
7
Institute of Computational Biotechnology, Graz University of Technology, Petersgasse 14/V, 8010 Graz, Austria
8
OMICS Center Graz, BioTechMed Graz, Stiftingtalstraße 24, 8010 Graz, Austria
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(19), 4740; https://doi.org/10.3390/ijms20194740
Received: 30 July 2019 / Revised: 19 September 2019 / Accepted: 21 September 2019 / Published: 24 September 2019
In tumor cells of more than 20 different cancer types, the CXCR4-CXCL12-axis is involved in multiple key processes including proliferation, survival, migration, invasion, and metastasis. Since data on this axis in diffuse large B cell lymphoma (DLBCL) are inconsistent and limited, we comprehensively studied the CXCR4-CXCL12-axis in our DLBCL cohort as well as the effects of CXCR4 antagonists on lymphoma cell lines in vitro. In DLBCL, we observed a 140-fold higher CXCR4 expression compared to non-neoplastic controls, which was associated with poor clinical outcome. In corresponding bone marrow biopsies, we observed a correlation of CXCL12 expression and lymphoma infiltration rate as well as a reduction of CXCR4 expression in remission of bone marrow involvement after treatment. Additionally, we investigated the effects of three CXCR4 antagonists in vitro. Therefore, we used AMD3100 (Plerixafor), AMD070 (Mavorixafor), and WKI, the niacin derivative of AMD070, which we synthesized. WK1 demonstrated stronger pro-apoptotic effects than AMD070 in vitro and induced expression of pro-apoptotic genes of the BCL2-family in CXCR4-positive lymphoma cell lines. Finally, WK1 treatment resulted in the reduced expression of JNK-, ERK1/2- and NF-κB/BCR-target genes. These data indicate that the CXCR4-CXCL12-axis impacts the pathogenesis of DLBCL and represents a potential therapeutic target in aggressive lymphomas. View Full-Text
Keywords: DLBCL 1; CXCR4-CXCL12-axis 2; CXCR4 antagonist 3 DLBCL 1; CXCR4-CXCL12-axis 2; CXCR4 antagonist 3
Show Figures

Graphical abstract

MDPI and ACS Style

Pansy, K.; Feichtinger, J.; Ehall, B.; Uhl, B.; Sedej, M.; Roula, D.; Pursche, B.; Wolf, A.; Zoidl, M.; Steinbauer, E.; Gruber, V.; Greinix, H.T.; Prochazka, K.T.; Thallinger, G.G.; Heinemann, A.; Beham-Schmid, C.; Neumeister, P.; Wrodnigg, T.M.; Fechter, K.; Deutsch, A.J. The CXCR4–CXCL12-Axis Is of Prognostic Relevance in DLBCL and Its Antagonists Exert Pro-Apoptotic Effects In Vitro. Int. J. Mol. Sci. 2019, 20, 4740.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop