Interleukin-12 and interleukin-18 synergistically induce murine tumor regression which involves inhibition of angiogenesis
Interleukin-12 and interleukin-18 synergistically induce murine tumor regression which involves inhibition of angiogenesis
复制标题
DOI：
10.1172/jci1555
复制
发表时间：
1998-03-15
影响因子：
15.9
通讯作者：
Lee, WMF
中科院分区：
文献类型：
--
作者：
Coughlin, CM;Salhany, KE;Lee, WMF
利用工程化SCK小鼠乳腺癌细胞研究了小鼠IL-12和IL-18（诱导IFN-γ产生的细胞因子）激活的抗肿瘤作用和机制。在同基因A/J小鼠中，表达mIL-12或mIL-18的SCK细胞的致瘤性较低，并且比对照细胞形成肿瘤更慢。SCK.12和SCK.18细胞均未显著保护远端SCK细胞的肿瘤发生。然而，两种细胞类型一起接种协同保护70%的小鼠免受同时注射的远距离SCK细胞的影响，30%的小鼠免受3天前建立的SCK细胞的影响。抗体中和研究表明，分泌的mIL-12和mIL-18的抗肿瘤作用需要IFN-γ。有趣的是，SCK.12和/或SCK.18细胞的一半存活者产生了保护性免疫，这表明抗SCK免疫不太可能负责保护。相反，通过Matrigel植入物测定的血管生成抑制似乎是SCK.12和SCK.18细胞的特性，并且两种细胞类型一起产生显著更大的血管生成全身抑制。这表明肿瘤血管生成的抑制是mIL-12和mIL-18产生的全身抗肿瘤作用的重要部分。
The antitumor effect and mechanisms activated by murine IL-12 and IL-18, cytokines that induce IFN-gamma production, were studied using engineered SCK murine mammary carcinoma cells, In syngeneic A/J mice, SCK cells expressing mIL-12 or mIL-18 were less tumorigenic and formed tumors more slowly than control cells. Neither SCK.12 nor SCK.18 cells protected significantly against tumorigenesis by distant SCK cells. However, inoculation of the two cell types together synergistically protected 70% of mice from concurrently injected distant SCK cells and 30% of mice from SCK cells established 3 d earlier, Antibody neutralization studies revealed that the antitumor effects of secreted mIL-12 and mIL-18 required IFN-gamma. Interestingly, half the survivors of SCK.12 and/or SCK.18 cells developed protective immunity suggesting that anti-SCK immunity is unlikely to be responsible for protection. Instead, angiogenesis inhibition, assayed by Matrigel implants, appeared to be a property of both SCK.12 and SCK.18 cells and the two cell types together produced significantly greater systemic inhibition of angiogenesis, This suggests that inhibition of tumor angiogenesis is an important part of the systemic antitumor effect produced by mIL-12 and mIL-18.