Giraldo G, Beth E, Hirshaut Y, Aoki T, Old L J, Boyse E A, Chopra H C
J Exp Med. 1971 Mar 1;133(3):454-78. doi: 10.1084/jem.133.3.454.
In a study of human sarcomas maintained in culture for periods up to two years, the following observations were made. The most prominent cell type in serially cultured osteosarcomas was fibroblastic in appearance. After 16-20 wk in culture some lines spontaneously developed foci of altered cells resembling the foci produced in monolayer cultures by oncogenic viruses. The presence of these foci in the sarcoma cultures was transient, and usually they did not reappear; but in one instance they recurred with a characteristic periodicity of several weeks. From one of the sarcoma lines, in which foci appeared after 5 months in culture, two subcultures were established from stored frozen cells and these both exhibited foci after approximately the same lapse of time. The same phenomenon has been seen with another line, suggesting that the time of appearance of foci is characteristic for particular sarcomas. Foci of similar type could sometimes be induced in monolayer cultures of human fibroblasts by filtered medium from cultured sarcomas; this bore no relation to the presence or absence of foci in the sarcoma cultures at the time the filtrate was prepared. Electron microscopy of the spontaneous and induced foci, and of the sarcoma cultures, revealed no demonstrable virus. 12 out of 15 sarcoma cultures contained an antigen (S) demonstrable by indirect immunofluorescence with human sera. It was not present in any of the original sarcoma specimens, nor in any culture lines other than sarcomas. At least 3-4 wk in culture appear to be required for its demonstration. The antigen was cytoplasmic, occurred in only a small proportion of the cells, and was unpredictably variable in its expression, even in the same culture line. It could be induced in monolayer cultures of human fibroblasts by filtrates of medium from sarcoma cultures. As with the foci, the induction of S antigen in indicator cultures was not dependent upon the expression of antigen in the sarcoma line from which the filtrates were obtained. There was no association between the presence of foci and of antigen, nor was there any apparent relation between the ability of filtrates to induce foci and their ability to induce antigen. 80% or more of the general population have S antibody, and the titer of antibody in patients with sarcoma is no higher than in normal subjects. Thus, as in the case of Burkitt's lymphoma antigen, it appears that most individuals have been exposed to S antigen. But unlike Burkitt's lymphoma, no relation has so far been established between any particular disease and a corresponding high titer or frequency of occurrence of S antibody. The occurrence of foci of altered cells and of a common antigen, and the transmission of these two characters to indicator cells by filtrates, are all suggestive of a virus specifically associated with human sarcomas, one to which the general population is widely exposed, as indicated by the prevalence of antibody.
在一项对人类肉瘤进行长达两年的培养研究中，有以下观察结果。连续培养的骨肉瘤中最突出的细胞类型外观呈成纤维细胞样。培养16 - 20周后，一些细胞系自发形成了细胞改变灶，类似于致癌病毒在单层培养中产生的病灶。肉瘤培养物中这些病灶的存在是短暂的，通常不会再次出现；但有一次它们以几周的特征性周期复发。从一个在培养5个月后出现病灶的肉瘤细胞系中，从储存的冻存细胞建立了两个亚培养物，这两个亚培养物在大致相同的时间间隔后都出现了病灶。在另一个细胞系中也观察到了同样的现象，这表明病灶出现的时间对于特定的肉瘤具有特征性。有时，来自培养肉瘤的过滤培养基可在人成纤维细胞的单层培养中诱导出类似类型的病灶；这与制备滤液时肉瘤培养物中是否存在病灶无关。对自发和诱导的病灶以及肉瘤培养物进行电子显微镜检查，未发现可证实的病毒。15个肉瘤培养物中有12个含有一种抗原（S），用人血清通过间接免疫荧光法可检测到。它在任何原始肉瘤标本中均不存在，除肉瘤外的任何培养细胞系中也不存在。培养至少3 - 4周似乎才能够检测到它。该抗原位于细胞质中，仅在一小部分细胞中出现，其表达不可预测地变化，即使在同一细胞系中也是如此。肉瘤培养物培养基的滤液可在人成纤维细胞的单层培养中诱导出该抗原。与病灶一样，指示培养物中S抗原的诱导并不依赖于获得滤液的肉瘤细胞系中抗原的表达。病灶的存在与抗原的存在之间没有关联，滤液诱导病灶的能力与其诱导抗原的能力之间也没有明显关系。80%或更多的普通人群具有S抗体，肉瘤患者的抗体滴度并不高于正常受试者。因此，如同伯基特淋巴瘤抗原的情况一样，似乎大多数个体都接触过S抗原。但与伯基特淋巴瘤不同的是，到目前为止，尚未在任何特定疾病与相应的高滴度S抗体或其出现频率之间建立联系。细胞改变灶和一种共同抗原的出现，以及这两个特征通过滤液传递给指示细胞，都提示存在一种与人类肉瘤特异性相关的病毒，正如抗体的普遍存在所表明的，普通人群广泛接触过这种病毒。
