Multifunctional interieukin-1β promotes metastasis of human lung cancer cells in SCID mice via enhanced expression of adhesion-, invasion- and angiogenesis-related molecules
Multifunctional interieukin-1β promotes metastasis of human lung cancer cells in SCID mice via enhanced expression of adhesion-, invasion- and angiogenesis-related molecules
复制标题
DOI：
10.1111/j.1349-7006.2003.tb01428.x
复制
发表时间：
2003-03-01
期刊：
影响因子：
5.7
通讯作者：
Sone, S
中科院分区：
文献类型：
--
作者：
Yano, S;Nokihara, H;Sone, S
我们检查了白细胞介素-1 (IL-1)（一种多功能促炎细胞因子）是否会促进或消退肺癌的转移。外源性 IL-10 增强表达 IL-1 受体的 A549、PC14、RERF-LC-A1 和 SBC-3 细胞各种细胞因子（IL-6、IL-8 和血管内皮生长因子 (VEGF)）和细胞内粘附分子 1 (ICAM-1) 的表达。用具有生长激素信号肽序列的人IL-1β基因转导的A549细胞（A549/IL-1β）分泌大量IL-1β蛋白。 IL-10 的过度表达导致细胞因子、ICAM-1 和基质金属蛋白酶-2 (MMP-2) 表达增加。与对照 A549 细胞相比，静脉注射 A549/IL-1β 细胞到严重联合免疫缺陷 (SCID) 小鼠体内的 A549/IL-1β 细胞更有效地分布到肺部，并且发生肺转移的速度更快。用抗IL-1β抗体治疗SCID小鼠可抑制A549/IL-1β细胞肺转移的形成。此外，与对照A549细胞相比，接种在皮下组织中的A549/IL-1β细胞生长更快，且没有坏死，对照A549细胞产生较小的肿瘤且中心坏死，这表明除了增强A549/IL-1β细胞的高转移潜力的结合外，还参与血管生成。组织学分析表明，与对照 A549 细胞衍生的肿瘤相比，在 A549/IL-1beta 细胞衍生的肿瘤中观察到更多的宿主细胞浸润、更少的凋亡细胞、更多的血管化和更高的 MMP 活性。这些发现表明，IL-1β 通过促进多种事件（包括粘附、侵袭和血管生成）来促进肺癌转移。
We examined whether interleukin-1 (IL-1), a multifunctional proinflammatory cytokine, progresses or regresses metastasis of lung cancer. Exogenous IL-10 enhanced expression of various cytokines (IL-6, IL-8, and vascular endothelial growth factor (VEGF)) and intracellular adhesion molecule-1 (ICAM-1) by A549, PC14, RERF-LC-A1, and SBC-3 cells expressing IL-1 receptors. A549 cells transduced with human IL-1beta-gene with the growth-hormone signaling-peptide sequence (A549/IL-1beta) secreted a large amount of IL-1beta protein. Overexpression of IL-10 resulted in augmentation of expression of the cytokines, ICAM-1, and matrix metalloproteinase-2 (MMP-2). A549/IL-1beta cells intravenously inoculated into severe combined immunodeficiency (SCID) mice distributed to the lung more efficiently and developed lung metastasis much more rapidly than did control A549 cells. Treatment of SCID mice with anti-IL-1beta antibody inhibited formation of lung metastasis by A549/IL-1beta cells. Moreover, A549/IL-1beta cells inoculated in the subcutis grew more rapidly, without necrosis, than did control A549 cells, which produced smaller tumors with central necrosis, suggesting involvement of angiogenesis in addition to enhanced binding in the high metastatic potential of A549/IL-1beta cells. Histological analyses showed that more host-cell infiltration, fewer apoptotic cells, more vascularization, and higher MMP activity were observed in tumors derived from A549/IL-1beta cells, compared with tumors derived from control A549 cells. These findings suggest that IL-1beta facilitates metastasis of lung cancer via promoting multiple events, including adhesion, invasion and angiogenesis.