| First Author | Daller B | Year | 2011 |
| Journal | Int J Cancer | Volume | 128 |
| Issue | 6 | Pages | 1363-70 |
| PubMed ID | 20473944 | Mgi Jnum | J:168819 |
| Mgi Id | MGI:4938265 | Doi | 10.1002/ijc.25456 |
| Citation | Daller B, et al. (2011) Lymphotoxin-beta receptor activation by lymphotoxin-alpha(1) beta(2) and LIGHT promotes tumor growth in an NFkappaB-dependent manner. Int J Cancer 128(6):1363-70 |
| abstractText | Lymphotoxin beta receptor (LTbetaR) 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 LTbetaR, namely LTalpha(1) beta(2) and LIGHT, are involved in the activation of LTbetaR in solid fibrosarcomas. To identify whether the lymphocyte population is involved in the activation of LTbetaR in these fibrosarcoma tumors, we used conditional LTbeta-deficient mice that specifically lack LTbeta expression either on T cells (T-LTbeta(-/-) ) or on B cells (B-LTbeta(-/-) ). 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 LTbetaR in these tumors. Tumor growth was also reduced in LIGHT-deficient mice, suggesting a contribution of this ligand to the activation of LTbetaR in BFS-1 fibrosarcomas. LTbetaR signaling can involve IkappaBalpha and/or NFkappaB-inducing kinase (NIK) for subsequent NFkappaB activation in different types of cells. Expression of a dominant negative form of IkappaBalpha or of a dominant negative mutant of NIK resulted in decreased activation of NFkappaB signaling and reduced expression of pro-angiogenic CXCL2 in vitro. Moreover, expression of dominant negative form of NIK or an IkappaBalpha repressor in these fibrosarcoma cells resulted in reduced solid tumor growth in vivo, suggesting that both IkappaBalpha and NIK are involved in pro-angiogenic signaling after LTbetaR activation. Our data support the idea that the ablation of LTbetaR signaling should be considered for cancer treatment. |
