Daller, Barbara and Muesch, Werner and Roehrl, Johann and Tumanov, Alexei V. and Nedospasov, Sergei A. and Maennel, Daniela N. and Schneider-Brachert, Wulf and Hehlgans, Thomas (2011) Lymphotoxin-beta receptor activation by lymphotoxin-alpha(1)beta(2) and LIGHT promotes tumor growth in an NF kappa B-dependent manner. INTERNATIONAL JOURNAL OF CANCER, 128 (6). pp. 1363-1370. ISSN 0020-7136,
Full text not available from this repository. (Request a copy)Abstract
Lymphotoxin beta receptor (LT beta R) activation on mouse fibrosarcoma cells (BFS-1) results in enhanced solid tumor growth paralleled by increased angiogenesis induced by the expression of pro-angiogenic CXCL2. In our study, we demonstrate that both functional ligands of the LT beta R, namely LT alpha(1)beta(2) and LIGHT, are involved in the activation of LT beta R in solid fibrosarcomas. To identify whether the lymphocyte population is involved in the activation of LT beta R in these fibrosarcoma tumors, we used conditional LT beta-deficient mice that specifically lack LT beta expression either on T cells (T-LT beta(-/-)) or on B cells (B-LT beta(-/-)). Solid tumor growth was reduced in both mouse strains when compared to tumor growth in wild-type mice, indicating the participation of both T and B host lymphocytes in the activation of LT beta R in these tumors. Tumor growth was also reduced in LIGHT-deficient mice, suggesting a contribution of this ligand to the activation of LT beta R in BFS-1 fibrosarcomas. LT beta R signaling can involve I kappa B alpha and/or NF kappa B-inducing kinase (NIK) for subsequent NF kappa B activation in different types of cells. Expression of a dominant negative form of I kappa B alpha or of a dominant negative mutant of NIK resulted in decreased activation of NF kappa B signaling and reduced expression of pro-angiogenic CXCL2 in vitro. Moreover, expression of dominant negative form of NIK or an I kappa B alpha repressor in these fibrosarcoma cells resulted in reduced solid tumor growth in vivo, suggesting that both I kappa B alpha and NIK are involved in pro-angiogenic signaling after LT beta R activation. Our data support the idea that the ablation of LT beta R signaling should be considered for cancer treatment.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MACROPHAGE INFLAMMATORY PROTEIN-2; LYMPHOID ORGANS; PATHWAYS; CELLS; TRANSCRIPTION; EXPRESSION; NECROSIS; MICE; ORGANOGENESIS; SUPERFAMILY; lymphotoxin beta receptor activation; NF kappa B signalling; CXCL2; tumor angiogenesis |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Immunologie Medicine > Lehrstuhl für Medizinische Mikrobiologie und Hygiene |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 24 Jun 2020 05:36 |
| Last Modified: | 24 Jun 2020 05:36 |
| URI: | https://pred.uni-regensburg.de/id/eprint/21115 |
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