| Autor: |
Vidal-Vanaclocha F, Alvarez A, Asumendi A, Urcelay B, Tonino P, Dinarello CA, Vidal-Vanaclocha, F, Alvarez, A, Asumendi, A, Urcelay, B, Tonino, P, Dinarello, C A |
| Zdroj: |
JNCI: Journal of the National Cancer Institute; 2/21/96, Vol. 88 Issue 3/4, p198-205, 8p |
| Abstrakt: |
Background: The growth of cancer cells in inflammatory tissue is often observed. This can be the result of favorable conditions for endothelial cell adherence and/or increased production of local growth factors.Purpose: The role of the proinflammatory cytokine interleukin 1 (IL-1) in the prometastatic and growth-promoting environment of inflammation was studied in vivo, and the mechanism of cytokine action was studied in vitro as well.Methods: Systemic inflammation was induced by the intravenous injection of IL-1 beta or lipopolysaccharide (LPS), and the hepatic metastasizing ability of B16 melanoma (B16) cells following intrasplenic injection was studied. IL-1 receptor blockade was accomplished with the use of the IL-1 receptor antagonist (IL-1Ra). In vitro, IL-1Ra was used to assess the mechanism for prometastasis and growth promotion of cultured hepatic sinusoidal endothelium stimulated with LPS.Results: There was a statistically significant (P < .01) enhancement in the parameters of hepatic metastasis when B16 cells were injected intrasplenically either 4 hours after IL-1 injection or 6 or 12 hours after LPS injection. IL-1Ra pretreatment reduced IL-1-induced enhancement of metastasis by 73%-87% and completely inhibited the augmentation of metastasis following LPS injection. In vitro, the adherence of melanoma cells to LPS-treated endothelium increased nearly twofold but was completely abrogated when IL-1Ra was added before LPS. Similar to melanoma adherence, a 2.5-fold increase (P < .05) in functional mannose receptors was observed with LPS treatment but was prevented by the addition of IL-1Ra did not affect basal mannose-receptor activity in unstimulated epithelium. Mannose-receptor activity and B16 cell adherence significantly correlated (r = .9) with LPS treatment. Conditioned medium from LPS-stimulated epithelium augmented B16 cell proliferation compared with control conditioned medium (P < .01). Production of B16 cell growth factor(s) was markedly reduced (P < .01) when IL-1Ra was added.Conclusions: These results demonstrate that systemic inflammation induces an enhancement of melanoma cell metastasis and growth by IL-1-dependent mechanisms in vivo. In vitro, the mechanism(s) is consistent with IL-1-mediated increase in expression of mannose receptors and production of tumor cell growth factor(s) from the endothelium.Implications: Given the multiple and complex cytokine cascade induced in vivo and in vitro during LPS-induced systemic inflammation, IL-1 plays a strategic role. Since IL-1Ra is without side effects in humans, studies on intraoperative infusion of IL-1Ra during tumor resection may be indicated. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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