REVERSAL OF THE METASTATIC PHENOTYPE IN LEWIS LUNG-CARCINOMA CELLS AFTER TRANSFECTION WITH SYNGENEIC H-2KB GENE

REVERSAL OF THE METASTATIC PHENOTYPE IN LEWIS LUNG-CARCINOMA CELLS AFTER TRANSFECTION WITH SYNGENEIC H-2KB GENE
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DOI:
10.1073/pnas.85.12.4463
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发表时间:
1988-06-01
影响因子:
11.1
通讯作者:
EISENBACH, L
EISENBACH, L
中科院分区:
综合性期刊1区
文献类型:
--
作者:
PLAKSIN, D;GELBER, C;EISENBACH, L

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小鼠3LL肿瘤高转移克隆的H-2kb主要组织相容性复合体I类抗原表达水平显著降低,而同一肿瘤的低转移克隆表达高水平的H-2kb。在H-2kb基因转染后诱导该抗原的表达导致转移表型转变为非转移表型或低转移表型。与亲本细胞不同,转基因细胞是H-2kb限制性同基因细胞毒淋巴细胞的有效诱导者,可以杀死KB阳性克隆并与亲本未转基因细胞发生交叉反应。用KB阳性的转染体预先免疫小鼠,可以防止恶性细胞的转移性扩散。此外,转移的免疫治疗是通过免疫H-2kb转基因细胞实现的,这些细胞已经携带了亲代细胞的局部生长的肿瘤。
High metastatic clones of the murine 3LL carcinoma express greatly reduced levels of H-2Kb major histocompatibility complex class I antigens, while low metastatic clones of the same tumor express high levels of H-2Kb. Induced expression of this antigen after transfection with the H-2Kb gene resulted in conversion of a metastatic to a non- or low-metastatic phenotype. Unlike the parental cells, transfected cells are potent inducers of H-2Kb-restricted syngeneic cytotoxic lymphocytes that kill the Kb-positive clones and cross-react with parental nontransfected cells. Preimmunization of mice with Kb-positive transfectants conferred protection against metastatic spread of malignant cells. Moreover, immunotherapy of metastasis was achieved by immunization with the H-2Kb-transfected cells of animals already carrying a growing local tumor of the parental cells.