| First Author | Vidal-Vanaclocha F | Year | 2000 |
| Journal | Proc Natl Acad Sci U S A | Volume | 97 |
| Issue | 2 | Pages | 734-9 |
| PubMed ID | 10639148 | Mgi Jnum | J:59893 |
| Mgi Id | MGI:1352275 | Doi | 10.1073/pnas.97.2.734 |
| Citation | Vidal-Vanaclocha F, et al. (2000) IL-18 regulates IL-1beta-dependent hepatic melanoma metastasis via vascular cell adhesion molecule-1. Proc Natl Acad Sci U S A 97(2):734-9 |
| abstractText | Proinflammatory cytokines, including IL-1beta and tumor necrosis factor-alpha (TNF-alpha), promote cancer cell adhesion and liver metastases by up-regulating the expression of vascular cell adhesion molecule-1 (VCAM-1) on hepatic sinusoidal endothelium (HSE). In this study, hepatic metastasis after intrasplenically injected mouse B16 melanoma (B16M) cells was reduced 84-95% in mice with null mutations for either IL-1beta or the IL-1beta-converting enzyme (ICE, caspase-1) compared with wild-type mice. On day 12, 47% of wild-type mice were dead compared with 19% of either IL-1beta or ICE-deficient mice. In vitro, conditioned medium from B16M cells (B16M-CM) induced the release of TNF-alpha and IL-1beta from cultures of primary murine HSE. The effect of B16M-CM on HSE resulted in increased numbers of B16M cells adhering to HSE, which was completely abrogated by a specific inhibitor of ICE, anti-IL-18 or IL-18-binding protein. Exogenous IL-18 added to HSE also increased the number of adhering melanoma cells; however, this was not affected by IL-1 receptor blockade or TNF neutralization but rather by anti-VCAM-1. These results demonstrate a role for IL-1beta and IL-18 in the development of hepatic metastases of B16M in vivo. In vitro, soluble products from B16M cells stimulate HSE to sequentially release TNF-alpha, IL-1beta, and IL-18. The IL-18 cytokine increases expression of VCAM-1 and the adherence of melanoma cells. |
