Elliott B E, Xu W, Mudrik K, Marshall J, Vekemans M, Holden J J
Cancer Research Laboratories, Queen's University, Kingston, Ontario, Canada.
Genes Chromosomes Cancer. 1992 Jun;4(4):281-9. doi: 10.1002/gcc.2870040403.
We have previously described a murine mammary tumor cell line (SP1) that metastasizes when transplanted into the mammary gland, but not when injected into the subcutaneous site. We used cytogenetic markers to assess genetic heterogeneity, and to monitor the selection and evolution of karyotypically distinct cell types during primary tumor growth and in metastases. The SP1 tumor cells are hypotetraploid (mean chromosome number = 72), and have at least four karyotypically distinct cell types. We found no consistent pattern of selection of tumor cell types in primary tumors. However, metastases were derived from a cell type that was present in the corresponding primary tumor. In addition, novel, karyotypically distinct cell types also appeared in the metastatic nodules. Markers that appeared in metastases included two translocations, t(10;18) and t(1;19). By injecting a mixture of cells from a metastatic nodule with a non-metastatic clone into mice, we showed that the new cell types in metastases displayed a stable increased growth and metastatic potential when compared to the non-metastatic clone, or when compared to the initial cell type from which the metastases derived. These results indicate that metastases are derived from a distinct cell type in the primary tumor, but that additional chromosome and cell evolution occurs, resulting in new cell types that are selected in metastases.
我们之前描述过一种小鼠乳腺肿瘤细胞系（SP1），将其移植到乳腺中时会发生转移，但注射到皮下部位时则不会转移。我们使用细胞遗传学标记来评估基因异质性，并监测原发性肿瘤生长和转移过程中核型不同的细胞类型的选择和进化。SP1肿瘤细胞为亚四倍体（平均染色体数 = 72），并且至少有四种核型不同的细胞类型。我们在原发性肿瘤中未发现肿瘤细胞类型选择的一致模式。然而，转移灶源自相应原发性肿瘤中存在的一种细胞类型。此外，核型不同的新细胞类型也出现在转移结节中。转移灶中出现的标记包括两个易位，即t(10;18)和t(1;19)。通过将转移结节中的细胞与非转移克隆细胞的混合物注射到小鼠体内，我们发现与非转移克隆相比，或者与转移灶所源自的初始细胞类型相比，转移灶中的新细胞类型显示出稳定增加的生长和转移潜力。这些结果表明，转移灶源自原发性肿瘤中一种独特的细胞类型，但会发生额外的染色体和细胞进化，从而产生在转移灶中被选择的新细胞类型。
