CC531s colon carcinoma cells induce apoptosis in rat hepatic endothelial cells by the Fas/FasL-mediated pathway
CC531s colon carcinoma cells induce apoptosis in rat hepatic endothelial cells by the Fas/FasL-mediated pathway
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DOI：
10.1034/j.1600-0676.2003.00840.x
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发表时间：
2003-08-01
影响因子：
6.7
通讯作者：
Braet, F
中科院分区：
文献类型：
--
作者：
Vekemans, K;Timmers, M;Braet, F
结直肠癌肝转移的机制尚不清楚。转移性结肠癌细胞比原发性结肠癌细胞表达更多的FasL，并且癌细胞通过Fas/FasL途径诱导肝细胞凋亡。因此，本研究重点关注大鼠肝窦内皮细胞（LSEC）和CC531s结肠癌细胞的体外和体内Fas/FasL表达和功能。 RT-PCR 和免疫化学分别揭示了 LSEC 和 CC531 中的 Fas 和 FasL。通过与含有或不含增强剂的人重组 FasL (1-100 ng/ml) 一起孵育，在体外评估 Fas 的功能。使用 Hoechst 33342/碘化丙啶染色和电子显微镜观察，在浓度为 10 ng/ml 和 100 ng/ml 的增强剂下，分别有 21% 和 44% 的内皮细胞显示出凋亡迹象。在共培养中，可以在 CC531 附近的内皮细胞中检测到细胞凋亡，并且可以被拮抗性 FasL 抗体抑制。此外，肠系膜注射 CC531 18 小时后，窦内皮显示破坏。总之，(i) CC531s 细胞利用 Fas/FasL 在体外诱导 LSEC 凋亡； (ii) CC531s 细胞损伤体内的窦内皮衬层； (iii) 这可能为 FasL 阳性肿瘤细胞提供通往肝细胞的门户。
The mechanisms involved in colorectal carcinoma with liver metastasis are not well known. Metastasizing colon carcinoma cells express more FasL than primary colon carcinoma cells and cancer cells induce apoptosis in hepatocytes by the Fas/FasL pathway. Therefore, this study focused on Fas/FasL expression and functionality in rat liver sinusoidal endothelial cells (LSECs) and CC531s colon carcinoma cells in vitro and in vivo . RT-PCR and immunochemistry revealed Fas and FasL in LSECs and CC531s, respectively. Functionality of Fas was assessed in vitro by incubation with human recombinant FasL (1-100 ng/ml) with or without enhancer. At concentrations of 10 and 100 ng/ml with enhancer, respectively 21% and 44% of endothelial cells showed signs of apoptosis using Hoechst 33342/propidium iodide staining and electron microscopy. In co-cultures, apoptosis could be detected in endothelial cells neighboring the CC531s and could be inhibited by an antagonistic FasL antibody. Moreover, 18 h after mesenteric injection of CC531s, the sinusoidal endothelium revealed disruption. In conclusion, (i) CC531s cells induce apoptosis in LSECs in vitro by using Fas/FasL; (ii) CC531s cells damage the sinusoidal endothelial lining in vivo ; and (iii) this might provide FasL-positive tumor cells a gateway towards the hepatocytes.