Sieweke M H, Stoker A W, Bissell M J
Division of Cell and Molecular Biology, Lawrence Berkeley Laboratory, University of California, Berkeley 94720.
Cancer Res. 1989 Nov 15;49(22):6419-24.
Chickens given injections of Rous sarcoma virus form sarcomas at the site of inoculation (primary tumor) and at the site of experimentally introduced wounds (wound tumor). This latter finding provides a model system to study systematically the mechanisms underlying the cocarcinogenic effects of wounding. Our experiments show the following. (a) Chickens inoculated with a Rous sarcoma virus-derived, replication-defective virus construct fail to elaborate wound tumors in spite of aggressively growing primary tumors. We thus rule out metastasis as a mechanism and conclude that infectious virus is required for wound tumor formation; (b) using bromodeoxyuridine incorporation and immunofluorescence on frozen sections we demonstrate proliferation in the unwounded wing in cell types which are normally targets for Rous sarcoma virus infection and transformation and conclude that proliferation per se is not sufficient to induce wound tumors; (c) using immunohistochemistry for the viral protein p19gag we show that wounding induces virus expression in fibroblasts of newly forming granulation tissue 2 days after injury. We also demonstrate expression of viral mRNA in wound tumors by in situ hybridization with a v-src probe. We discuss the possibility of activation of integrated, silent virus or the preferential infection of a special target cell population as a result of wounding as well as the potential role of wound factors in transformation.
注射劳斯肉瘤病毒的鸡在接种部位（原发性肿瘤）和实验性创伤部位（创伤性肿瘤）形成肉瘤。后一发现提供了一个模型系统，用于系统研究创伤协同致癌作用的潜在机制。我们的实验结果如下：（a）接种劳斯肉瘤病毒衍生的复制缺陷型病毒构建体的鸡，尽管原发性肿瘤生长旺盛，但未能形成创伤性肿瘤。因此，我们排除了转移作为一种机制，并得出结论，创伤性肿瘤的形成需要感染性病毒；（b）通过在冰冻切片上使用溴脱氧尿苷掺入和免疫荧光，我们证明了在未受伤的翅膀中，正常情况下是劳斯肉瘤病毒感染和转化靶标的细胞类型发生了增殖，并得出结论，增殖本身不足以诱导创伤性肿瘤；（c）使用针对病毒蛋白p19gag的免疫组织化学方法，我们发现创伤在损伤后2天诱导新形成的肉芽组织中的成纤维细胞表达病毒。我们还通过与v-src探针的原位杂交在创伤性肿瘤中证明了病毒mRNA的表达。我们讨论了创伤导致整合的沉默病毒激活或特殊靶细胞群体优先感染的可能性，以及创伤因子在转化中的潜在作用。
