Monoclonal antibodies that prevent adhesion of B 16 melanoma cells and reduce metastases in mice: crossreaction with human tumor cells.

Monoclonal antibodies that prevent adhesion of B 16 melanoma cells and reduce metastases in mice: crossreaction with human tumor cells.
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防止 B 16 黑色素瘤细胞粘附并减少小鼠转移的单克隆抗体:与人类肿瘤细胞的交叉反应。

DOI:
10.1073/pnas.80.22.6863
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发表时间:
1983
影响因子:
11.1
通讯作者:
W. Birchmeier
W. Birchmeier
中科院分区:
综合性期刊1区
文献类型:
--
作者:
H. Vollmers;W. Birchmeier

文献摘要

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在同基因小鼠中针对B16黑色素瘤细胞产生的单克隆抗体,就其在组织培养中抑制细胞黏附的能力进行了功能性筛选。当将其中三种抗体(16/43、16/77、16/82)预先注射到C57BL/6小鼠体内时,显著减少了B16细胞产生的实验性肺转移数量,可能是通过干扰它们与肺内皮细胞的黏附。我们现在报道,这些单克隆抗体在体外阻断了所测试的大多数人黑色素瘤细胞系以及来自小鼠和人类的癌细胞、神经母细胞瘤细胞和胶质母细胞瘤细胞的黏附,但未转化的细胞系,如3T3小鼠或MRC - 5人成纤维细胞不受影响。这些抗体也与小鼠畸胎瘤干细胞(F9、PCC4)发生反应,但不与分化的畸胎瘤细胞系(PYS - 2、944)反应。此外,抗体的抗黏附活性可被完整的人和小鼠肿瘤细胞定量吸收,但不被未转化的细胞吸收,这表明相应的抗原可能代表肿瘤相关的细胞表面成分。相应地,在猿猴病毒40转化的3T3小鼠成纤维细胞上发现了这些抗原,并且在由温度敏感型劳斯肉瘤病毒转化的鸡成纤维细胞中以温度敏感的方式表达。在含十二烷基硫酸钠的凝胶的“免疫印迹”中,三种选定的抗体(16/43、16/82、19/1)被分子量为40,000和50,000的抗原吸收。
Monoclonal antibodies raised against B 16 melanoma cells in syngeneic mice were functionally screened for their ability to inhibit cell adhesion in tissue culture. Three of these antibodies (16/43, 16/77, 16/82), when preinjected into C57BL/6 mice, markedly reduced the number of experimental lung metastases produced by B 16 cells, possibly by interference with their adhesion to the lung endothelia. We now report that these monoclonal antibodies block in vitro attachment of the majority of human melanoma cell lines tested and also of carcinoma, neuroblastoma, and glioblastoma cells from both mice and humans but untransformed cell lines such as 3T3 mouse or MRC-5 human fibroblasts are not affected. The antibodies also react with mouse teratocarcinoma stem cells (F9, PCC4) but not with differentiated teratocarcinoma lines (PYS-2, 944). Furthermore, the antiadhesion activity of the antibodies could be quantitatively absorbed by intact human and mouse tumor cells but not by untransformed cells, suggesting that the corresponding antigens may represent tumor-associated cell surface components. Correspondingly, the antigens were found on simian virus 40-transformed 3T3 mouse fibroblasts and are expressed in a temperature-sensitive fashion in chicken fibroblasts transformed with a temperature-sensitive Rous sarcoma virus. On "immunoblots" of NaDodSO4-containing gels the three selected antibodies (16/43, 16/82, 19/1) were absorbed by antigens with molecular weights of 40,000 and 50,000.