Mannori G, Santoro D, Carter L, Corless C, Nelson R M, Bevilacqua M P
Howard Hughes Medical Institute, University of California, San Diego, La Jolla, USA.
Am J Pathol. 1997 Jul;151(1):233-43.
During metastasis, tumor cells adhere to vascular endothelia. E-selectin is an adhesive protein expressed by cytokine-activated endothelium that can support adhesion of colon cancer cells through the recognition of specific carbohydrate ligands. Using a series of colon carcinoma cell lines that displayed E-selectin adhesiveness and an increased metastatic capacity in cytokine-treated mice, we examined possible inhibition of cytokine-dependent experimental lung metastasis by a soluble form of E-selectin, the recombinant fusion protein E-selectin-immunoglobulin. We found that E-selectin-immunoglobulin bound to the surfaces of HT-29 colon carcinoma cells and blocked the formation of cytokine-inducible experimental lung metastases; control L-selectin-immunoglobulin also bound to HT-29 cells but had no effect on tumor cell lung colonization. E-selectin-immunoglobulin was found to interfere with E-selectin-dependent adhesion of HT-29 cells to activated vascular endothelium and to block the retention of these cells in the lung, a process that implies tumor cell adhesive interactions with the host vasculature. Our results demonstrate that E-selectin-immunoglobulin inhibits adhesion and formation of lung metastases by colon carcinoma cells and suggest that impairment of tumor cell-endothelium adhesion might represent a therapeutic approach to the metastatic diffusion of tumors.
在转移过程中，肿瘤细胞会黏附于血管内皮。E-选择素是一种由细胞因子激活的内皮细胞表达的黏附蛋白，它可通过识别特定的碳水化合物配体来支持结肠癌细胞的黏附。利用一系列在细胞因子处理的小鼠中表现出E-选择素黏附性且转移能力增强的结肠癌细胞系，我们研究了可溶性形式的E-选择素（重组融合蛋白E-选择素-免疫球蛋白）对细胞因子依赖性实验性肺转移的可能抑制作用。我们发现E-选择素-免疫球蛋白结合到HT-29结肠癌细胞表面，并阻断了细胞因子诱导的实验性肺转移的形成；对照L-选择素-免疫球蛋白也结合到HT-29细胞上，但对肿瘤细胞在肺部的定植没有影响。研究发现E-选择素-免疫球蛋白会干扰HT-29细胞与活化血管内皮的E-选择素依赖性黏附，并阻止这些细胞在肺部的滞留，这一过程意味着肿瘤细胞与宿主脉管系统之间存在黏附相互作用。我们的结果表明，E-选择素-免疫球蛋白可抑制结肠癌细胞肺转移的黏附与形成，并提示肿瘤细胞-内皮细胞黏附的受损可能是一种针对肿瘤转移扩散的治疗方法。
