Cohen S A, Goldrosen M H
Department of Medicine, VA Medical Center, Buffalo, NY 14215.
Immunol Invest. 1989 Jan-May;18(1-4):351-63. doi: 10.3109/08820138909112248.
Although numerous animal tumor models have been used to study colon carcinoma, few display hepatic metastasis. C57B1/6Ros mice inoculated with liver-derived murine colon adenocarcinoma MCA-38 in the ileocolic vein develop distinct hepatic foci within 21 days and survive an average of 35 days. Furthermore, 111In-labeled LD-MCA-38 tumor cells were rapidly taken up by the liver within 60 min and 73% of the label remained in the liver after 24 h. Isolated nonparenchymal liver cells from untreated mice displayed little cytotoxicity against freshly excised 51Cr-labeled MCA-38 cells but did inhibit tumor growth in vitro as measured by inhibition of 3H-thymidine incorporation. Treatment with anti-asialo-GM1 decreased the lifespan of MCA-38 tumor bearing mice suggesting that asialo-GM1 positive cells in the liver may inhibit tumor growth in vivo. Nonparenchymal liver cells from mice treated with polyinosinic-polycytidylic acid showed augmented cytotoxic and cytostatic activity against LD-MCA-38 tumor cells in vitro. Polyinosinic-polycytidylic acid treatment also significantly increased the lifespan of MCA-38 tumor bearing mice. In conclusion, the host defense system of the liver can be modulated to enhance or inhibit colon-derived experimental hepatic metastasis.
尽管众多动物肿瘤模型已被用于研究结肠癌,但很少有模型会出现肝转移。通过回结肠静脉接种源自肝脏的小鼠结肠腺癌MCA-38的C57B1/6Ros小鼠,在21天内会形成明显的肝病灶,平均存活35天。此外,111In标记的LD-MCA-38肿瘤细胞在60分钟内被肝脏迅速摄取,24小时后73%的标记物仍留在肝脏中。从未经处理的小鼠中分离出的非实质肝细胞对新鲜切除的51Cr标记的MCA-38细胞几乎没有细胞毒性,但通过抑制3H-胸腺嘧啶核苷掺入法测定,其在体外确实能抑制肿瘤生长。用抗唾液酸GM1治疗会缩短携带MCA-38肿瘤小鼠的寿命,这表明肝脏中唾液酸GM1阳性细胞可能在体内抑制肿瘤生长。用聚肌苷酸-聚胞苷酸处理的小鼠的非实质肝细胞在体外对LD-MCA-38肿瘤细胞显示出增强的细胞毒性和细胞生长抑制活性。聚肌苷酸-聚胞苷酸处理还显著延长了携带MCA-38肿瘤小鼠的寿命。总之,肝脏的宿主防御系统可以被调节,以增强或抑制源自结肠的实验性肝转移。