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克隆化人肺癌细胞系的肿瘤内表型多样性及其对单克隆抗体分析的影响

Intratumoral phenotypic diversity of cloned human lung tumor cell lines and consequences for analyses with monoclonal antibodies.

作者信息

Olsson L, Sorensen H R, Behnke O

出版信息

Cancer. 1984 Nov 1;54(9):1757-65. doi: 10.1002/1097-0142(19841101)54:9<1757::aid-cncr2820540902>3.0.co;2-5.

DOI:10.1002/1097-0142(19841101)54:9<1757::aid-cncr2820540902>3.0.co;2-5
PMID:6089998
Abstract

Cloned cell lines and a number of subclones from these lines were established in vitro from biopsies of small cell lung carcinomas and squamous cell lung carcinomas. The cloned cultures, including the cloned subclones, were analyzed in respect to morphology, karyotype, growth rates, clonogenicity in semisolid agar medium, and tumorigenicity in nude mice. A remarkable biologic diversity was found in respect to most of these biologic features. In addition, four murine monoclonal antibodies with high specificity for lung tumor cells were generated. Their reactivity pattern to clonogenic cells was for some clones different as compared to the nonclonogenic cells. Subclones of tumor cells not binding the antibody were identified for each monoclonal antibody. It is concluded that intratumoral phenotypic diversity may have a severe negative impact on the use of monoclonal antibodies in cancer diagnosis/therapy. The work also indicates that a mixture of antibodies may be more useful in tumor diagnosis than individual antibodies and perhaps even therapy, particularly if they bind to the clonogenic part of a cell population.

摘要

从小细胞肺癌和肺鳞状细胞癌活检组织中体外建立了克隆细胞系以及这些细胞系的多个亚克隆。对克隆培养物,包括克隆亚克隆,进行了形态学、核型、生长速率、半固体琼脂培养基中的克隆形成能力以及裸鼠致瘤性分析。在这些生物学特性的大多数方面发现了显著的生物学多样性。此外,制备了四种对肺肿瘤细胞具有高特异性的鼠单克隆抗体。与非克隆形成细胞相比,它们对某些克隆的克隆形成细胞的反应模式有所不同。针对每种单克隆抗体鉴定出不与该抗体结合的肿瘤细胞亚克隆。得出的结论是,肿瘤内表型多样性可能对单克隆抗体在癌症诊断/治疗中的应用产生严重负面影响。这项工作还表明,抗体混合物在肿瘤诊断中可能比单个抗体更有用,甚至在治疗中也是如此,特别是如果它们与细胞群体的克隆形成部分结合。

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Intratumoral phenotypic diversity of cloned human lung tumor cell lines and consequences for analyses with monoclonal antibodies.克隆化人肺癌细胞系的肿瘤内表型多样性及其对单克隆抗体分析的影响
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Intracerebral and subcutaneous xenografts of human SCLC in the nude rat: comparison of monoclonal antibody localization and tumor infiltrating lymphocytes.人小细胞肺癌在裸鼠体内的脑内和皮下异种移植:单克隆抗体定位与肿瘤浸润淋巴细胞的比较
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Tumorigenic human squamous lung cancer cells have defined cell surface carbohydrates that are absent from nontumorigenic cells.
致瘤性人肺鳞状癌细胞具有特定的细胞表面碳水化合物,而非致瘤性细胞则没有。
Proc Natl Acad Sci U S A. 1988 Feb;85(3):802-6. doi: 10.1073/pnas.85.3.802.
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