Cancer Therapy and Research Center; Shandong Provincial Hospital; Shandong University; Jinan, PR China.
Cancer Biol Ther. 2014 Jun 1;15(6):789-96. doi: 10.4161/cbt.28552. Epub 2014 Mar 21.
Systemic inflammation might modulate the microenvironment in the lungs and promotes metastasis. E-selectin, an inflammation inducible endothelial cell adhesion molecule, has been reported to play an important role in homing metastatic cancer cells. To study the effects of E-selectin expression induced by systemic inflammation on breast cancer metastasis, we first treated BALB/c mice with lipopolysaccharide (LPS) to induce systemic inflammation. Pulmonary tissues were analyzed by wet/dry ratio, hematoxylin and eosin (H&E) staining and immunohistochemistry. Then 4T1 cells were injected via tail vein. Lung surface metastasis was counted and detected by histological analysis. LPS-induced E-selectin expression and tumor cells adhesion were assessed by western blotting and immunofluorescence. The circulating levels of proinflammatory cytokines in sera were evaluated by ELISA. Our results showed that a significant increase in breast cancer metastasis to lungs was observed in LPS-treated mice vs. the PBS-treated mice, accompanying with an increased E-selectin expression in pulmonary tissue of LPS-treated mice. In vitro studies showed a significant elevation of E-selectin production in MPVECs which enhanced the adhesion activity of 4T1 cells. Treatment with anti-E-selectin antibody significantly reduced the development of metastasis in vivo, and significantly reduced the adhesion of 4T1 cells to MPVECs in vitro. Our results suggest that systemic inflammation may increase the expression of E-selectin which mediated the lung metastasis of breast cancer in mouse model.
系统性炎症可能调节肺部的微环境，并促进转移。E-选择素，一种炎症诱导的内皮细胞黏附分子，已被报道在归巢转移性癌细胞中发挥重要作用。为了研究系统性炎症诱导的 E-选择素表达对乳腺癌转移的影响，我们首先用脂多糖（LPS）处理 BALB/c 小鼠以诱导系统性炎症。通过湿/干比、苏木精和伊红（H&E）染色和免疫组织化学分析肺组织。然后通过尾静脉注射 4T1 细胞。通过组织学分析计数和检测肺表面转移。通过 Western blot 和免疫荧光评估 LPS 诱导的 E-选择素表达和肿瘤细胞黏附。通过 ELISA 评估血清中促炎细胞因子的循环水平。我们的结果表明，与 PBS 处理的小鼠相比，LPS 处理的小鼠中乳腺癌转移到肺部的明显增加，同时 LPS 处理的小鼠肺组织中 E-选择素表达增加。体外研究表明，MPVECs 中 E-选择素的产生显著升高，增强了 4T1 细胞的黏附活性。体内用抗 E-选择素抗体治疗显著减少了转移的发展，体外也显著减少了 4T1 细胞与 MPVECs 的黏附。我们的结果表明，系统性炎症可能增加 E-选择素的表达，从而介导乳腺癌在小鼠模型中的肺转移。
