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Lymphotoxin-beta receptor activation by lymphotoxin-alpha(1)beta(2) and LIGHT promotes tumor growth in an NF kappa B-dependent mannerстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 18 июля 2013 г.
- Авторы: Daller Barbara, Muesch Werner, Roehrl Johann, Tumanov Alexei V., Nedospasov Sergei A., Maennel Daniela N., Schneider-Brachert Wulf, Hehlgans Thomas
- Журнал: International Journal of Cancer
- Том: 128
- Номер: 6
- Год издания: 2011
- Издательство: John Wiley & Sons Inc.
- Местоположение издательства: United States
- Первая страница: 1363
- Последняя страница: 1370
- DOI: 10.1002/ijc.25456
- Аннотация: 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.
- Добавил в систему: Недоспасов Сергей Артурович