Complement-mediated killing of microtumors in vitro
Complement-mediated killing of microtumors in vitro
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DOI：
10.1016/s0002-9440(10)65626-x
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发表时间：
1998-09-01
影响因子：
6
通讯作者：
Meri, S
中科院分区：
文献类型：
--
作者：
Hakulinen, J;Meri, S
在三维聚集体中生长的癌细胞的补体介导的裂解涉及与杀死悬浮液中的细胞无关的因素。我们已经使用了从乳腺癌（T47 D）和卵巢畸胎瘤（PA-1）细胞系建立的多细胞肿瘤球体作为模型来研究补体介导的微转移和小实体瘤的破坏。我们发现用抗肿瘤抗体和针对补体裂解抑制剂保护素（CD 59）的特异性单克隆抗体（YTH 53.1）处理的微肿瘤的显著杀伤在1至2小时的滞后期后开始发生。过夜孵育后，微肿瘤被YTH 53.1单克隆抗体和C1 q完全浸润，而C3和C5 b-9作为边界渗透到外周细胞层。Cr-51释放测定显示，在用补体脉冲处理24小时期间，球状体中33%的细胞被杀死，平均肿瘤体积减小28%。根据碘化丙啶染色，补体暴露导致最外层肿瘤细胞的杀伤和剥离。
Complement-mediated lysis of cancer cells growing in three-dimensional aggregates involves factors that are not associated with the killing of cells in suspension. We have used multicellular tumor spheroids established from breast carcinoma (T47D) and ovarian teratocarcinoma (PA-1) cell lines as models to study complement-mediated destruction of micrometastases and small solid tumors. We found that significant killing of microtumors treated with an antitumor antibody and a specific monoclonal antibody (YTH53.1) against the complement lysis inhibitor protectin (CD59) started to occur after a 1 to 2-hour lag phase. After an overnight incubation, the microtumors became totally infiltrated by the YTH53.1 monoclonal antibody and C1q, whereas C3 and C5b-9 penetrated as a frontier to the peripheral cell layers. A Cr-51 release assay showed that during a 24-hour pulsed treatment with complement, 33% of cells in the spheroids were killed, and the average tumor volume decreased by 28%. According to propidium iodide staining, complement exposure resulted in killing and peeling off of the outermost tumor cells.