Induction of the metastatic phenotype in a mouse tumor model by 5-azacytidine, and characterization of an antigen associated with metastatic activity.
Induction of the metastatic phenotype in a mouse tumor model by 5-azacytidine, and characterization of an antigen associated with metastatic activity.
复制标题
5-氮杂胞苷在小鼠肿瘤模型中诱导转移表型，以及与转移活性相关的抗原的表征。
DOI：
10.1073/pnas.81.11.3389
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发表时间：
1984
影响因子：
11.1
通讯作者：
J. Forchhammer
中科院分区：
文献类型：
--
作者：
L. Olsson;J. Forchhammer
小鼠刘易斯肺癌是一种长期移植肿瘤，皮下接种后，形成肺转移。从原发性肿瘤部位建立42个细胞系，从肺转移灶建立40个细胞系。从82个原始细胞系中建立了克隆的亚系，在405个亚系中发现2个亚系是致瘤性的但不转移（T+/M-），而其余403个亚系是致瘤性和转移性的（T+/M+）。T+/M-表型显示稳定超过2年。然而，用3 μ M 5-氮杂胞苷处理T+/M-细胞系3天导致转移表型在其他稳定的T+/M-细胞系中重新表达。此外，5-氮杂胞苷处理可导致稳定的T+/M+细胞系转移表型的丧失。肿瘤发生和转移表型的变化与细胞免疫原性的改变无关。产生了针对T+/M+细胞的单克隆抗体，并且发现一种抗体（M36 D3）仅结合T+/M+细胞。发现抗体的反应性与转移表型的表达共变。因此，M36 D3抗体识别的抗原似乎与转移能力相关。通过二维凝胶电泳分析发现抗原是一种细胞蛋白，其Mr约等于45，000，pI约等于6.7。
The murine Lewis lung carcinoma is a long-term grafted tumor that, after subcutaneous inoculation, forms metastases to the lungs. Forty-two cell lines were established from a primary tumor site and 40 were established from lung metastatic foci. Cloned sublines were established from the original 82 lines, and 2 sublines among 405 were found to be tumorigenic but not metastatic (T+/M-), whereas the remaining 403 sublines were both tumorigenic and metastatic (T+/M+). The T+/M- phenotype was shown to be stable for greater than 2 yr. However, treatment of the T+/M- cell lines for 3 days with 3 microM 5-azacytidine resulted in reexpression of the metastatic phenotype in otherwise stable T+/M- lines. Also, 5-azacytidine treatment could result in loss of the metastatic phenotype in lines that had been stable T+/M+. The changes in tumorigenic and metastatic phenotypes were not associated with altered immunogenicity of the cells. Monoclonal antibodies were generated against T+/M+ cells, and one antibody ( M36D3 ) was found to bind only to T+/M+ cells. Reactivity of the antibody was found to co-vary with expression of the metastatic phenotype. The antigen recognized by M36D3 antibody thus seems to be associated with metastatic capability. The antigen was found by two-dimensional gel electrophoretic analysis to be a cellular protein of Mr approximately equal to 45,000 and pI approximately equal to 6.7.