Talmadge J E, Fidler I J
J Natl Cancer Inst. 1982 Oct;69(4):975-80.
These studies demonstrated that cells populating spontaneous metastases are, in general, more metastatic than the cells populating the parent neoplasm, thereby providing direct evidence that the process of metastasis is selective and not random. The tumors used in these studies were the UV-2237 fibrosarcoma, an in vitro cloned line (C-40) from the UV-2237 tumor, and the K-1735 melanoma, all of which are syngeneic to the C3H/HeN (mammary tumor virus-negative) mouse strain; the M5076 reticulum cell sarcoma and the Lewis lung carcinoma 3LL, which are syngeneic to the C57BL/6 mouse strain, were also used. All tumors were implanted sc into the footpads of syngeneic mice, and several resulting spontaneous metastases were isolated and established in culture as individual cell lines. For each tumor system, comparison was made of the ability of parent tumor cells and cells isolated from several spontaneous metastases to produce either experimental or spontaneous metastases. Cells populating spontaneous metastases produced by heterogeneous and poorly metastatic tumors were significantly more metastatic than the cells of their respective parent tumors. In contrast, cells populating metastases produced by previously selected tumors did not differ significantly in metastatic potential from cells populating their parent tumors. In such systems, metastasis appeared to be random.
这些研究表明，构成自发性转移灶的细胞通常比构成原发肿瘤的细胞具有更强的转移能力，从而提供了直接证据，证明转移过程是选择性的而非随机的。这些研究中使用的肿瘤包括UV-2237纤维肉瘤、来自UV-2237肿瘤的体外克隆系（C-40）以及K-1735黑色素瘤，所有这些肿瘤均与C3H/HeN（乳腺肿瘤病毒阴性）小鼠品系同基因；还使用了与C57BL/6小鼠品系同基因的M5076网状细胞肉瘤和Lewis肺癌3LL。所有肿瘤均皮下植入同基因小鼠的足垫，从产生的几个自发性转移灶中分离出细胞，并作为单个细胞系进行培养。对于每个肿瘤系统，比较了原发肿瘤细胞和从几个自发性转移灶中分离出的细胞产生实验性或自发性转移的能力。由异质性和低转移性肿瘤产生的自发性转移灶中的细胞比其各自原发肿瘤的细胞具有显著更强的转移能力。相比之下，请点击此处添加原文中未翻译的内容，由先前选择的肿瘤产生的转移灶中的细胞与构成其原发肿瘤的细胞在转移潜力上没有显著差异。在这样的系统中，转移似乎是随机的。
