Department of Gastroenterology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom.
Clin Cancer Res. 2013 Apr 1;19(7):1693-704. doi: 10.1158/1078-0432.CCR-12-2940. Epub 2013 Feb 11.
Cytokines such as interleukin (IL)-6 and granulocyte colony-stimulating factor (G-CSF) are important metastasis promoters. This study has investigated the functional significance of the increased circulation of galectin-3, a common feature in patients with cancer 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 patients with colorectal cancer with and without metastasis was investigated.
Galectin-3 at pathologic concentrations found in patients with cancer induces secretion of IL-6, G-CSF, sICAM-1, and granulocyte macrophage colony-stimulating factor 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 integrinα(v)β(1), 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 patients with cancer 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 patients with cancer therefore represents a promising therapeutic strategy to reduce metastasis and improve survival.
细胞因子，如白细胞介素（IL）-6 和粒细胞集落刺激因子（G-CSF）是重要的转移促进剂。本研究调查了在癌症患者中常见的循环半乳糖凝集素-3（galectin-3）增加对血管内皮细胞从血液中分泌细胞因子的功能意义，特别是在那些有转移的患者中。
通过细胞因子阵列评估 galectin-3 在体外对人微血管肺内皮细胞分泌细胞因子的影响，并在小鼠体内进行评估。确定 galectin-3 诱导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循环 galectin-3 与细胞因子水平之间的关系。
在癌症患者中发现的病理性浓度的 galectin-3 诱导体外和小鼠体内血管内皮细胞分泌 IL-6、G-CSF、sICAM-1 和粒细胞巨噬细胞集落刺激因子。这些细胞因子自分泌/旁分泌相互作用于血管内皮细胞，增加内皮细胞表面粘附分子整合素α（v）β（1）、E-选择素、ICAM-1 和 VCAM-1 的表达，导致癌细胞-内皮细胞粘附增加和内皮细胞迁移和小管形成增加。在转移性结直肠癌患者中，血清 galectin-3 水平升高与血清 G-CSF、IL-6 和 sICAM1 浓度升高显著相关。
癌症患者循环 galectin-3 的增加诱导血管内皮细胞分泌几种促进转移的细胞因子，增强转移中的内皮细胞活性。因此，针对癌症患者循环 galectin-3 的作用代表了一种有前途的治疗策略，可以减少转移并提高生存率。
