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融合诱导的恶性肿瘤?一项初步研究。(对当今普遍认知的挑战)

Fusion-induced malignancy? A preliminary study. (a challenge to today's common wisdom).

作者信息

Munzarová M, Lauerová L, Kovarík J, Rejthar A, Brezina V, Kellnerová R, Kovarík A

机构信息

Masaryk Memorial Cancer Institute, Brno, Czechoslovakia.

出版信息

Neoplasma. 1992;39(2):79-86.

PMID:1528312
Abstract

Five fusions between mouse embryonic cells and syngeneic adult peritoneal macrophages were performed. The resulting hybrids as well as both parental cells (6 cultures of embryonal cells and 6 cultures of adult macrophages) were grown in vitro under the same culture conditions. All populations of explanted macrophages died during the second month in primary culture and five populations of cultured embryonic cells were lost within six months under in vitro conditions as well. One embryonic cell line survived and acquired transformed and/or malignant phenotype: When inoculated into either newborn or adult syngeneic mice, progressive growth of tumors with 100% take (6/6), histologically classified as poorly differentiated fibrosarcoma with areas of metaplastic bone and osteoid, was observed. Two out of five wild hybrid strains died within six months of cell culture. The resulting three hybrid cultures adapted themselves to in vitro conditions and finally permanent lines were established with all features of transformed phenotype in vitro and with the capacity to grow as undifferentiated fibrosarcomas with 100% take (6/6) when inoculated into syngeneic mice either s.c. or i.p. Cytogenetic studies were performed and phenotypic characteristics of these lines were explored as well. Biological assays performed for the presence of oncogenic viruses were negative and none of the malignant cell lines showed positive staining with the monoclonal antibody specific for large T-antigen. It is suggested that cell fusion of two normal partners may switch on the cascade of abnormal processes which may culminate in neoplastic conversion. Cell fusion might play also a significant role in the so called "spontaneous" transformation.

摘要

进行了五次小鼠胚胎细胞与同基因成年腹膜巨噬细胞的融合。将所得杂种细胞以及两种亲代细胞(6种胚胎细胞培养物和6种成年巨噬细胞培养物)在相同培养条件下进行体外培养。所有移出的巨噬细胞群体在原代培养的第二个月死亡,5种培养的胚胎细胞群体在体外条件下6个月内也全部丢失。一种胚胎细胞系存活下来并获得了转化和/或恶性表型:当接种到新生或成年同基因小鼠体内时,观察到肿瘤进行性生长,接种成功率为100%(6/6),组织学分类为低分化纤维肉瘤,伴有化生骨和类骨质区域。五个野生杂种细胞系中有两个在细胞培养6个月内死亡。所得的三个杂种细胞培养物适应了体外条件,最终建立了永久细胞系,这些细胞系在体外具有转化表型的所有特征,接种到同基因小鼠皮下或腹腔时能够以100%的成功率(6/6)生长为未分化纤维肉瘤。进行了细胞遗传学研究,并探索了这些细胞系的表型特征。针对致癌病毒存在情况进行的生物学检测结果为阴性,且没有一个恶性细胞系用针对大T抗原的单克隆抗体显示阳性染色。提示两个正常细胞的融合可能开启一系列异常过程,最终可能导致肿瘤转化。细胞融合在所谓的“自发”转化中可能也起重要作用。

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