Yano S, Nokihara H, Hanibuchi M, Parajuli P, Shinohara T, Kawano T, Sone S
Third Department of Internal Medicine, University of Tokushima School of Medicine, Japan.
Oncol Res. 1997;9(11-12):573-9.
Malignant pleural effusion (PE) is a frequent problem in lung cancer. In this study, we established a model of malignant PE of human adenocarcinoma cells, PC-14, in SCID mice. Intravenously injected PC-14 cells formed colonies in the lungs as early as week 4 after tumor inoculation, and produced bloody PE in all recipient SCID mice by week 8. Pretreatment of SCID mice with anti-mouse IL-2 receptor beta chain antibody (TM-beta 1) to deplete natural killer (NK) cells markedly promoted the production of bloody PE and metastases to multiple organs, such as the lungs, liver, kidneys, and lymph nodes 4 weeks after tumor inoculation. Histological studies indicated that PC-14 cells formed colonies in the lungs, and then invaded the pleura and spread to the pleural cavity. To establish cell lines with a high potential to produce PE, we harvested PE, expanded the tumor cells in vitro, and injected them into SCID mice again. By four in vivo selection cycles in this way we obtained PC-14-PM4 cells, which produce lung metastases and PE earlier than PC-14 cells. The survival of SCID mice inoculated with PC-14-PM4 cells was significantly shorter than that of mice inoculated with PC-14 cells. The expressions of adhesion molecules, such as CD44, CD49d, ICAM-1, and MHC class I, on PC-14-PM4 cells tended to increase compared with PC-14 cells. These changes of adhesion molecules seem to be one of possible mechanisms involved in higher metastatic potential of PC-14-PM4 cells. PE models with PC-14 and PC-14-PM4 cells should be useful for biological and preclinical studies on malignant PE produced by human lung cancer.
恶性胸腔积液（PE）是肺癌中常见的问题。在本研究中，我们在SCID小鼠中建立了人腺癌细胞PC - 14的恶性PE模型。静脉注射PC - 14细胞在肿瘤接种后第4周就开始在肺部形成菌落，并在第8周时在所有受体SCID小鼠中产生血性胸腔积液。用抗小鼠IL - 2受体β链抗体（TM - β1）预处理SCID小鼠以耗尽自然杀伤（NK）细胞，在肿瘤接种后4周显著促进了血性胸腔积液的产生以及向多个器官（如肺、肝、肾和淋巴结）的转移。组织学研究表明，PC - 14细胞在肺部形成菌落，然后侵入胸膜并扩散到胸腔。为了建立具有高产生胸腔积液潜力的细胞系，我们收集胸腔积液，在体外扩增肿瘤细胞，然后再次将其注射到SCID小鼠体内。通过这种方式进行四个体内选择周期，我们获得了PC - 14 - PM4细胞，其产生肺转移和胸腔积液的时间比PC - 14细胞更早。接种PC - 14 - PM4细胞的SCID小鼠的存活时间明显短于接种PC - 14细胞的小鼠。与PC - 14细胞相比，PC - 14 - PM4细胞上的粘附分子如CD44、CD49d、ICAM - 1和MHC I类分子的表达倾向于增加。这些粘附分子的变化似乎是PC - 14 - PM4细胞具有更高转移潜力的可能机制之一。PC - 14和PC - 14 - PM4细胞的胸腔积液模型应该有助于对人肺癌产生的恶性胸腔积液进行生物学和临床前研究。
