Okuno Kiyotaka, Kawai Isao, Hirai Norihiko, Narimatsu Hisashi, Yasutomi Masayuki
First Department of Surgery, Kinki University School of Medicine, 377-2 Ohno-higashi, Osaka-sayama 589-8511, Japan.
Hepatogastroenterology. 2003 May-Jun;50(51):756-60.
BACKGROUND/AIMS: As sialyl Lewis X is a lignad of the selectin family, it has been proposed that sialyl Lewis X-rich colon cancer cells metastasize to the liver by adhesion to selectins on hepatic endothelial cells. However, little is known about the interaction between sialyl Lewis X and hepatic immune cells. We evaluated the role of sialyl Lewis X in liver metastasis in view of liver-associated immunity.
RCN-9, a colonic cancer cell line derived from Fischer rats, and its subclone RCN-H4, which exhibited high metastatic potential to the liver, were used. In an attempt to investigate the underlying basis for the difference in hepatic metastasis formation, we assessed the susceptibility of both cell lines to lysis by hepatic sinusoidal lymphocytes in 51Cr-release assays, and the expression of a number of carbohydrate antigens by both cell lines by flow cytometry.
Hepatic sinusoidal lymphocytes mainly consist of natural cytotoxic lymphocytes, including NKT cells. The H4 colonic cancer subclone showed decreased susceptibility to lysis by hepatic sinusoidal lymphocytes, as compared to the parent cell line. In addition, a significant increase of sialyl Lewis X expression was noted in the H4 subclone. Neuraminidase treatment of H4 cells increased their susceptibility to hepatic sinusoidal lymphocyte-mediated killing. Furthermore, rats inoculated with neuraminidase-treated H4 cells produced fewer metastatic nodules in the liver than those inoculated with untreated H4 cells.
Sialyl Lewis X expression in tumor cells reduced their susceptibility to hepatic sinusoidal lymphocyte-mediated killing, and thus, may facilitate the ability of the tumor cells to metastasize to the liver.
背景/目的：由于唾液酸化路易斯X是选择素家族的一种配体，有人提出富含唾液酸化路易斯X的结肠癌细胞通过黏附于肝内皮细胞上的选择素而转移至肝脏。然而，关于唾液酸化路易斯X与肝免疫细胞之间的相互作用却知之甚少。我们从肝脏相关免疫的角度评估了唾液酸化路易斯X在肝转移中的作用。
使用源自Fischer大鼠的结肠癌细胞系RCN-9及其对肝脏具有高转移潜能的亚克隆RCN-H4。为了探究肝转移形成差异的潜在基础，我们在51Cr释放试验中评估了这两种细胞系对肝窦淋巴细胞裂解的敏感性，并通过流式细胞术评估了这两种细胞系中多种碳水化合物抗原的表达。
肝窦淋巴细胞主要由包括NKT细胞在内的自然细胞毒性淋巴细胞组成。与亲代细胞系相比，H4结肠癌细胞亚克隆对肝窦淋巴细胞裂解的敏感性降低。此外，在H4亚克隆中观察到唾液酸化路易斯X表达显著增加。用神经氨酸酶处理H4细胞可增加其对肝窦淋巴细胞介导杀伤的敏感性。此外，接种经神经氨酸酶处理的H4细胞的大鼠肝脏中产生的转移瘤结节比接种未经处理的H4细胞的大鼠少。
肿瘤细胞中唾液酸化路易斯X的表达降低了它们对肝窦淋巴细胞介导杀伤的敏感性，因此可能促进肿瘤细胞转移至肝脏的能力。
