Kikkawa H, Miyamoto D, Imafuku H, Koike C, Suzuki Y, Okada S, Tsukada H, Irimura T, Oku N
Department of Radiobiochemistry, School of Pharmaceutical Sciences, University of Shizuoka.
Jpn J Cancer Res. 1998 Dec;89(12):1296-305. doi: 10.1111/j.1349-7006.1998.tb00527.x.
To elucidate the early events of blood-borne metastasis under actual blood flow, real-time trafficking of RAW117 large cell lymphoma cells, namely parental RAW117-P and liver-metastatic RAW117-H10 cells, was investigated using positron emission tomography (PET). Both types of cells accumulated in the liver immediately after injection via the portal vein, and were eliminated from the liver time-dependently. The elimination rate of RAW117-H10 cells, however, was slower than that of RAW117-P cells, suggesting that RAW117-H10 cells interact more strongly with hepatic sinusoidal endothelium than the parental cells. This result correlated with the metastatic potential of these cells: RAW117-H10 cells metastasized in the liver to a greater extent than RAW117-P cells after injection via this route. To investigate the role of sialylglycoconjugates in the interaction of RAW117-H10 cells with the hepatic endothelium after injection via the portal vein, the trafficking of RAW117-H10 cells was examined after the cells had been treated with sialidase. The elimination rate of RAW117-H10 cells from liver was observed to be greatly accelerated by sialidase treatment. To elucidate what kind of sialylglycoconjugates is related to this phenomenon, we analyzed the distribution of sialyl Lewis A and sialyl Lewis X antigens of both sublines of RAW117 by using flow cytometry. RAW117-H10 cells were found to express a much higher level of sialyl Lewis A than RAW117-P cells, whereas the amount of sialyl Lewis X did not differ significantly. These findings suggest that some sialylglycoconjugates, perhaps sialyl Lewis A in particular, play an important role in the initial interaction of RAW117-H10 cells with the hepatic endothelium, leading to metastasis.
为了阐明在实际血流情况下血行转移的早期事件,利用正电子发射断层扫描(PET)研究了RAW117大细胞淋巴瘤细胞,即亲本RAW117-P细胞和肝转移性RAW117-H10细胞的实时转运情况。两种类型的细胞经门静脉注射后立即在肝脏中聚集,并随时间从肝脏中清除。然而,RAW117-H10细胞的清除率比RAW117-P细胞慢,这表明RAW117-H10细胞与肝窦内皮的相互作用比亲本细胞更强。这一结果与这些细胞的转移潜能相关:经此途径注射后,RAW117-H10细胞在肝脏中的转移程度比RAW117-P细胞更大。为了研究唾液酸糖缀合物在经门静脉注射后RAW117-H10细胞与肝内皮相互作用中的作用,在用唾液酸酶处理细胞后检测了RAW117-H10细胞的转运情况。观察到唾液酸酶处理可大大加速RAW117-H10细胞从肝脏的清除率。为了阐明哪种唾液酸糖缀合物与这一现象相关,我们使用流式细胞术分析了RAW117两个亚系的唾液酸路易斯A和唾液酸路易斯X抗原的分布。发现RAW117-H10细胞比RAW117-P细胞表达更高水平的唾液酸路易斯A,而唾液酸路易斯X的量没有显著差异。这些发现表明,一些唾液酸糖缀合物,特别是唾液酸路易斯A,在RAW117-H10细胞与肝内皮的初始相互作用中起重要作用,从而导致转移。