Matsumura Hideki, Kondo Tadashi, Ogawa Koichi, Tamura Takafumi, Fukunaga Kiyoshi, Murata Soichiro, Ohkohchi Nobuhiro
Department of Surgery, Doctoral Program in Clinical Science, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki 305‑8575, Japan.
Int J Oncol. 2014 Dec;45(6):2303-10. doi: 10.3892/ijo.2014.2662. Epub 2014 Sep 18.
Although Kupffer cells (KCs) play an important role in the liver's immune response, their role in colon cancer metastasis to the liver is unclear. We here analyzed the relationship between KCs and tumor cells (TCs) in colon cancer metastasis to the liver. Fischer 344 (F344) rats were divided into control group (KC+ group) and KC elimination group (KC‑ group), in which KC elimination was induced by Cl2MDP liposome injection. RCN‑H4 colon cancer cells were injected into the rats of both groups, and the relationship between the two types of cells was observed by intravital microscopy (IVM) for 6 h. Moreover, to investigate the effect of KCs on liver metastasis formation, KCs were eliminated at different time points before and after the TC injection. The number of metastatic nodules 2 weeks after the injection was evaluated. In the KC‑ group, IVM revealed that the number of adherent TCs had increased 1.5‑fold at 6 h after the TC injection as compared with in the KC+ group. Moreover, in the KC+ group, 74% of the TCs adhered to the KCs, and KC activation and KC phagocytosis of the TCs were observed. Two weeks after the injection, the number of metastatic nodules was significantly increased in rats in which the KCs had been eliminated before the injection, but not in rats in which the KCs had been eliminated after the injection. KC activation and KC phagocytosis of TCs decreased colon cancer cell metastasis to the liver.
尽管库普弗细胞(KCs)在肝脏免疫反应中发挥重要作用,但其在结肠癌肝转移中的作用尚不清楚。我们在此分析了KCs与结肠癌肝转移中肿瘤细胞(TCs)之间的关系。将Fischer 344(F344)大鼠分为对照组(KC+组)和KC清除组(KC-组),其中通过注射氯膦酸二钠脂质体诱导KC清除。将RCN-H4结肠癌细胞注射到两组大鼠体内,通过活体显微镜(IVM)观察6小时,以观察两种细胞之间的关系。此外,为了研究KCs对肝转移形成的影响,在TC注射前后的不同时间点清除KCs。评估注射后2周转移结节的数量。在KC-组中,IVM显示,与KC+组相比,TC注射后6小时贴壁TC的数量增加了1.5倍。此外,在KC+组中,74%的TCs粘附于KCs,并观察到KC对TCs的激活和吞噬作用。注射后2周,在注射前清除KCs的大鼠中转移结节的数量显著增加,但在注射后清除KCs的大鼠中未增加。KC对TCs的激活和吞噬作用减少了结肠癌细胞向肝脏的转移。