Fogler W E, Fidler I J
Cancer Res. 1985 Jan;45(1):14-8.
The purpose of these studies was to select in vitro tumor cells that were resistant to macrophage-mediated lysis. Seven different heterogeneous murine neoplasms (four fibrosarcomas, a melanoma, a rhabdomyosarcoma, and an osteogenic sarcoma) and one cloned line of a fibrosarcoma were incubated in vitro with syngeneic tumoricidal macrophages. Surviving tumor cells were recovered and expanded to undergo subsequent interaction with tumoricidal macrophages. After six sequential interactions, all cell lines were examined for their susceptibility to lysis mediated by murine peritoneal exudate macrophages activated with liposomes containing muramyl tripeptide phosphatidylethanolamine. In all eight systems, no significant differences were detected between the parent tumor cells and cells that survived the sequential interactions. Neither macrophage infiltration into s.c. tumors nor the experimental or spontaneous metastatic potentials of the parental tumors differed from the lines established by cells surviving macrophage-mediated lysis. Collectively, the data suggest that tumor cell destruction by activated macrophages is nonselective and does not lead to the development of resistant tumor cells nor to cells with altered metastatic properties.
这些研究的目的是筛选出对巨噬细胞介导的裂解具有抗性的体外肿瘤细胞。将七种不同的异质性小鼠肿瘤(四种纤维肉瘤、一种黑色素瘤、一种横纹肌肉瘤和一种骨肉瘤)以及一种纤维肉瘤的克隆系与同基因的杀肿瘤巨噬细胞在体外共同孵育。回收存活的肿瘤细胞并进行扩增,以便随后与杀肿瘤巨噬细胞进行相互作用。经过六次连续相互作用后,检测所有细胞系对由含有胞壁酰三肽磷脂酰乙醇胺的脂质体激活的小鼠腹腔渗出巨噬细胞介导的裂解的敏感性。在所有八个系统中,未检测到亲本肿瘤细胞与经连续相互作用后存活的细胞之间存在显著差异。巨噬细胞向皮下肿瘤的浸润以及亲本肿瘤的实验性或自发性转移潜能与通过存活于巨噬细胞介导的裂解的细胞建立的细胞系均无差异。总体而言,数据表明活化巨噬细胞对肿瘤细胞的破坏是非选择性的,不会导致抗性肿瘤细胞的产生,也不会导致具有改变的转移特性的细胞的产生。