Matsushita Y, Kitajima S, Goto M, Tezuka Y, Sagara M, Imamura H, Tanabe G, Tanaka S, Aikou T, Sato E
Department of Pathology II, Faculty of Medicine, Kagoshima University, Japan.
Cancer Lett. 1998 Nov 27;133(2):151-60. doi: 10.1016/s0304-3835(98)00220-1.
We have previously reported that colon cancer cells metastasized to the liver expressed an increased amount of sialyl Lewis X (SLeX) antigen compared to their corresponding primary lesions. It is now well known that SLeX antigen and sialyl Lewis A (SLeA) antigen are ligands for the selectins expressed on the endothelial cells. Therefore, it is assumed that SLeX-rich colon cancer cells could be easily adhered to the endothelial cells that express selectins. In this report we have tried to induce selectin expression on the human liver sinusoidal endothelial cells and have examined the adhesion of SLeX-high or -low expressing colon cancer cells to the interleukin-1beta (IL-1beta)-treated liver specimens using Stamper-Woodruff assay. These human colon cancer cells are termed KM12HX or KM12LX cells, respectively. A significantly increased number of KM12HX cells adhered to the IL-1beta-treated liver specimens compared to KM12LX cells. The adhesion of KM12HX cells was inhibited by the pretreatment of tumor cells with anti-SLeX antibody or by the pretreatment of liver specimens with anti-selectin antibodies. Selectin expression on the liver sinusoidal endothelial cells and endothelial cells of blood vessels after IL-1beta treatment was confirmed by immunohistochemically using anti-selectin monoclonal antibodies (MAbs). These findings strongly suggest that SLeX-expressing cancer cells could adhere to the sinusoidal endothelial cells via an SLeX-selectin interaction system and this could be a first step for colon cancer cells that metastasize to the liver. The mechanism by which these selectins can be induced in vivo is the next problem to be considered.
我们之前报道过，与相应的原发性病灶相比，转移至肝脏的结肠癌细胞表达的唾液酸化路易斯X（SLeX）抗原量增加。现在已知SLeX抗原和唾液酸化路易斯A（SLeA）抗原是内皮细胞上表达的选择素的配体。因此，可以推测富含SLeX的结肠癌细胞能够轻易黏附于表达选择素的内皮细胞。在本报告中，我们试图诱导人肝窦内皮细胞表达选择素，并使用斯坦珀-伍德拉夫试验检测高表达或低表达SLeX的结肠癌细胞与白细胞介素-1β（IL-1β）处理的肝脏标本的黏附情况。这些人结肠癌细胞分别称为KM12HX或KM12LX细胞。与KM12LX细胞相比，黏附于IL-1β处理的肝脏标本的KM12HX细胞数量显著增加。用抗SLeX抗体预处理肿瘤细胞或用抗选择素抗体预处理肝脏标本可抑制KM12HX细胞的黏附。用抗选择素单克隆抗体（MAb）进行免疫组织化学证实了IL-1β处理后肝窦内皮细胞和血管内皮细胞上选择素的表达。这些发现强烈表明，表达SLeX的癌细胞可通过SLeX-选择素相互作用系统黏附于肝窦内皮细胞，这可能是结肠癌细胞转移至肝脏的第一步。这些选择素在体内可被诱导的机制是接下来需要考虑的问题。
