Increased circulation of galectin-3 in cancer induces secretion of metastasis-promoting cytokines from blood vascular endothelium.
Increased circulation of galectin-3 in cancer induces secretion of metastasis-promoting cytokines from blood vascular endothelium.
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DOI：
10.1158/1078-0432.ccr-12-2940
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发表时间：
2013-04-01
期刊：
影响因子：
--
通讯作者：
Yu LG
中科院分区：
文献类型：
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作者：
Chen C;Duckworth CA;Zhao Q;Pritchard DM;Rhodes JM;Yu LG
细胞因子如IL-6和G-CSF是重要的转移促进剂。本研究调查了半乳糖凝集素-3循环增加对癌症血管内皮细胞分泌细胞因子的功能意义，半乳糖凝集素-3是癌症患者，特别是转移患者的常见特征。通过细胞因子阵列在体外和在小鼠体内评估半乳糖凝集素-3对人微血管肺内皮细胞分泌细胞因子的影响。测定半乳糖凝集素-3诱导的细胞因子分泌对内皮细胞行为的影响，并研究有和无转移的结直肠癌患者中循环半乳糖凝集素-3和细胞因子水平之间的关系。在癌症患者中发现的病理浓度的半乳糖凝集素-3在体外和小鼠中诱导血液血管内皮细胞分泌IL-6、G-CSF、sICAM-1和GM-CSF。这些细胞因子自分泌/旁分泌与血管内皮相互作用，增加内皮细胞表面粘附分子整合素αvβ1、E-选择素、ICAM-1和VCAM-1的表达，导致癌细胞-内皮粘附增加，内皮细胞迁移和小管形成增加。在转移性结肠癌患者中，血清半乳糖凝集素-3水平升高与血清G-CSF、IL-6和sICAM 1浓度升高显著相关。癌症患者中半乳糖凝集素-3循环的增加诱导从血液血管内皮分泌几种促进转移的细胞因子，其增强转移中的内皮细胞活性。因此，靶向癌症患者中循环半乳糖凝集素-3的作用代表了减少转移和提高存活率的有希望的治疗策略。
Cytokines such as IL-6 and G-CSF are important metastasis promoters. This study has investigated the functional significance of the increased circulation of galectin-3, a common feature in cancer patients and in particular those with metastasis, on cytokine secretion from the blood vascular endothelium in cancer. The effects of galectin-3 on secretion of cytokines from human microvascular lung endothelial cells were assessed in vitro by cytokine array and in vivo in mice. The consequences of galectin-3-induced cytokine secretion on endothelial cell behaviors were determined and the relationship between the levels of circulating galectin-3 and cytokines in colorectal cancer patients with and without metastasis was investigated. Galectin-3 at pathological concentrations found in cancer patients induces secretion of IL-6, G-CSF, sICAM-1 and GM-CSF from blood vascular endothelial cells in vitro and in mice. These cytokines autocrinely/paracrinely interact with the vascular endothelium to increase the expressions of endothelial cell surface adhesion molecules integrinαvβ1, E-selectin, ICAM-1 and VCAM-1, resulting in increased cancer cell-endothelial adhesion and increased endothelial cell migration and tubule formation. In patients with metastatic colon cancer, higher serum galectin-3 levels correlated significantly with increased serum G-CSF, IL-6 and sICAM1 concentrations. The increased circulation of galectin-3 in cancer patients induces secretion of several metastasis-promoting cytokines from the blood vascular endothelium that enhances endothelial cell activities in metastasis. Targeting the actions of circulating galectin-3 in cancer patients therefore represents a promising therapeutic strategy to reduce metastasis and improve survival.