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- W2213561640 abstract "Chronic lymphocytic leukemia (CLL) is an incurable malignancy of B lymphocytes that accumulate in blood, bone marrow, and secondary lymphoid organs. Signals from the lymphoid tumor microenvironment are known to critically influence the pathogenesis of CLL by stimulating tumor cell proliferation and survival. In consequence, localization of CLL cells within this environment contributes to residual disease after therapy and to the development of a chemoresistant phenotype. The chemokine stromal-cell derived factor 1 (SDF-1, CXCL12), produced by stromal cells and other accessory cells in the bone marrow and lymph nodes, has a key role in protective CLL cell-microenvironment interactions. We found that CXCL12-induced integrin activation is essential for the capacity of CLL cells to home to the bone marrow. Ligation of the corresponding chemokine receptor CXCR4, which is highly expressed in CLL, rapidly activates VLA-4 on CLL cells resulting in their arrest on VCAM-1 substrates under shear flow. Here, we found that CLL cells express CXCR3. CXCR3 engagement by its ligands CXCL9, CXCL10 or CXCL11 diminishes CLL cell interactions with the VCAM-1/CXCL12 substrate under shear conditions. Moreover, chemotaxis to CXCL12 is significantly reduced in the presence of the CXCR3 ligands whereby the CXCR4 surface levels are not altered. Notably, CXCR3 does not affect CCR7-mediated chemotaxis to CCL19, suggesting a specific CXCR3-CXCR4 crosstalk in CLL migration and adhesion. CLL cell proliferation is not influenced by the presence of CXCR3 ligands, and since CXCR4 is entirely downregulated in proliferating CLL cells, a CXCR4-CXCR3 crosstalk in this process is unlikely. However, survival benefits provided by CXCL12 are partially abolished by co-incubation of the CLL cells with CXCL11. Collectively, our data point to a crosstalk of CXCR3 and CXCR4 that might be based on their heterodimerization, which is currently investigated." @default.
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- W2213561640 date "2013-09-01" @default.
- W2213561640 modified "2023-09-27" @default.
- W2213561640 title "88" @default.
- W2213561640 doi "https://doi.org/10.1016/j.cyto.2013.06.091" @default.
- W2213561640 hasPublicationYear "2013" @default.
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