Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Pansy, K; Feichtinger, J; Ehall, B; Uhl, B; Sedej, M; Roula, D; Pursche, B; Wolf, A; Zoidl, M; Steinbauer, E; Gruber, V; Greinix, HT; Prochazka, KT; Thallinger, GG; Heinemann, A; Beham-Schmid, C; Neumeister, P; Wrodnigg, TM; Fechter, K; Deutsch, AJ.
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(19):
Doi: 10.3390/ijms20194740
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- Führende Autor*innen der Med Uni Graz
- Deutsch Alexander
- Pansy Katrin
- Co-Autor*innen der Med Uni Graz
- Beham-Schmid Christine
- Ehall Barbara
- Fechter Karoline
- Feichtinger Julia
- Greinix Hildegard
- Heinemann Akos
- Neumeister Peter
- Prochazka Katharina
- Roula David
- Sedej Miriam
- Steinbauer Elisabeth
- Uhl Barbara
- Wolf Axel
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- Abstract:
- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Antineoplastic Agents - pharmacology
- Apoptosis - drug effects
- Biomarkers -
- Cell Line, Tumor -
- Cell Movement - drug effects
- Cell Proliferation - drug effects
- Chemokine CXCL12 - genetics
- Chemokine CXCL12 - metabolism
- Exons -
- Female -
- Gene Expression -
- Heterocyclic Compounds, 1-Ring - pharmacology
- Humans -
- Lymphoma, Large B-Cell, Diffuse - metabolism
- Lymphoma, Large B-Cell, Diffuse - mortality
- Lymphoma, Large B-Cell, Diffuse - pathology
- Male -
- Mutation -
- Neoplasm Staging -
- Prognosis -
- Receptors, CXCR4 - antagonists & inhibitors
- Receptors, CXCR4 - genetics
- Receptors, CXCR4 - metabolism
- Signal Transduction - drug effects
- Find related publications in this database (Keywords)
- DLBCL 1
- CXCR4-CXCL12-axis 2
- CXCR4 antagonist 3