Cohen S A, Tzung S P, Doerr R J, Goldrosen M H
Department of Medicine, VA Medical Center, Buffalo, New York 14215.
Cancer Res. 1990 Mar 15;50(6):1834-40.
Liver-derived (LD) murine colon adenocarcinoma MCA-38 cells injected into the ileocolic vein (ICV) of C57BL/6 mice developed distinct hepatic foci within 14-21 days and survived for an average of 19-35 days. In contrast, C57BL/6-nu/nu mice given injections of LD-MCA cells by the same route did not develop hepatic lesions. Furthermore, 111In-labeled LD-MCA-38 tumor cells were rapidly taken up by the liver of conventional mice within 1 h and 73% of the radioactivity remained after 24 h. However, about 60% of the 111In-labeled LD-MCA-38 tumor cells were cleared from the liver of nude mice after 24 h. Nonparenchymal liver cells isolated from untreated conventional mice displayed little cytotoxicity against freshly excised 51Cr-labeled LD-MCA-38 cells but did lyse the standard natural killer target, YAC-1 tumor cells, in 4 h chromium release assays. On the other hand, nonparenchymal liver cells but not spleen cells from nude mice were cytotoxic to 51CR-labeled LD-MCA-38 in vitro. The nonparenchymal liver cell population responsible for tumor killing was phenotypically nonadherent and asialo-GM1 (AsGM1) positive. C57BL/6 mice treated with polyinosinic-polycytidylic acid [poly(IC)] also displayed cytotoxic activity against LD-MCA-38 tumor cells in vitro. Furthermore, poly(IC) treatment of mice 1-8 days after tumor inoculation suppressed the number of hepatic foci and also significantly increased the life span of tumor-bearing mice. Treatment of athymic nude mice or poly(IC)-treated conventional mice with anti-AsGM1 induced significant numbers of foci and significantly decreased the life span of MCA-38-bearing mice suggesting that AsGM1-positive cells in the liver of these mice may inhibit tumor growth in vivo. In conclusion, the host defense system of the liver from athymic nude or poly(IC)-treated mice possess AsGM1-positive cells that can suppress tumor implantation or tumor growth in the early stages of metastasis in liver.
将源自肝脏（LD）的小鼠结肠腺癌MCA - 38细胞注入C57BL / 6小鼠的回结肠静脉（ICV）后，在14 - 21天内形成了明显的肝病灶，平均存活19 - 35天。相比之下，通过相同途径注射LD - MCA细胞的C57BL / 6 - nu / nu小鼠未出现肝脏病变。此外，111In标记的LD - MCA - 38肿瘤细胞在1小时内被正常小鼠的肝脏迅速摄取，24小时后仍有73%的放射性残留。然而，24小时后，约60%的111In标记的LD - MCA - 38肿瘤细胞从小鼠肝脏中清除。从未经处理的正常小鼠分离出的非实质肝细胞对新鲜切除的51Cr标记的LD - MCA - 38细胞几乎没有细胞毒性，但在4小时的铬释放试验中确实能裂解标准的自然杀伤靶细胞YAC - 1肿瘤细胞。另一方面，来自裸鼠的非实质肝细胞而非脾细胞在体外对51CR标记的LD - MCA - 38具有细胞毒性。负责杀伤肿瘤的非实质肝细胞群体在表型上不黏附且无唾液酸GM1（AsGM1）阳性。用聚肌苷酸 - 聚胞苷酸[poly(IC)]处理的C57BL / 6小鼠在体外也对LD - MCA - 38肿瘤细胞表现出细胞毒性活性。此外，在肿瘤接种后1 - 8天用poly(IC)处理小鼠可抑制肝病灶数量，并显著延长荷瘤小鼠的寿命。用抗AsGM1处理无胸腺裸鼠或用poly(IC)处理的正常小鼠会诱导大量病灶形成，并显著缩短荷MCA - 38小鼠的寿命，这表明这些小鼠肝脏中的AsGM1阳性细胞可能在体内抑制肿瘤生长。总之，无胸腺裸鼠或用poly(IC)处理的小鼠肝脏的宿主防御系统拥有AsGM1阳性细胞，这些细胞可在肝脏转移的早期阶段抑制肿瘤植入或肿瘤生长。
