Heinig, Kristina and Gaetjen, Marcel and Grau, Michael and Stache, Vanessa and Anagnostopoulos, Ioannis and Gerlach, Kerstin and Niesner, Raluca A. and Cseresnyes, Zoltan and Hauser, Anja E. and Lenz, Peter and Hehlgans, Thomas and Brink, Robert and Westermann, Joerg and Doerken, Bernd and Lipp, Martin and Lenz, Georg and Rehm, Armin and Hoepken, Uta E. (2014) Access to Follicular Dendritic Cells Is a Pivotal Step in Murine Chronic Lymphocytic Leukemia B-cell Activation and Proliferation. CANCER DISCOVERY, 4 (12). pp. 1448-1465. ISSN 2159-8274, 2159-8290
Full text not available from this repository. (Request a copy)Abstract
In human chronic lymphocytic leukemia (CLL) pathogenesis, B-cell antigen receptor signaling seems important for leukemia B-cell ontogeny, whereas the microenvironment influences B-cell activation, tumor cell lodging, and provision of antigenic stimuli. Using the murine E mu-Tcl1 CLL model, we demonstrate that CXCR5-controlled access to follicular dendritic cells confers proliferative stimuli to leukemia B cells. Intravital imaging revealed a marginal zone B cell-like leukemia cell trafficking route. Murine and human CLL cells reciprocally stimulated resident mesenchymal stromal cells through lymphotoxin-beta-receptor activation, resulting in CXCL13 secretion and stromal compartment remodeling. Inhibition of lymphotoxin/lymphotoxin-beta-receptor signaling or of CXCR5 signaling retards leukemia progression. Thus, CXCR5 activity links tumor cell homing, shaping a survival niche, and access to localized proliferation stimuli. SIGNIFICANCE: CLL and other indolent lymphoma are not curable and usually relapse after treatment, a process in which the tumor microenvironment plays a pivotal role. We dissect the consecutive steps of CXCR5-dependent tumor cell lodging and LT beta R-dependent stroma-leukemia cell interaction; moreover, we provide therapeutic solutions to interfere with this reciprocal tumor-stroma cross-talk. (C) 2014 AACR.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | SECONDARY LYMPHOID ORGANS; CHEMOKINE RECEPTORS; GENE-EXPRESSION; GERMINAL CENTER; STROMAL CELLS; CLL; LYMPHOTOXIN; MIGRATION; ZONE; MICROENVIRONMENT; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Immunologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 07 Aug 2019 09:06 |
| Last Modified: | 07 Aug 2019 09:06 |
| URI: | https://pred.uni-regensburg.de/id/eprint/9122 |
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