Selective events in the metastatic process defined by analysis of the sequential dissemination of subpopulations of a mouse mammary tumor.
Selective events in the metastatic process defined by analysis of the sequential dissemination of subpopulations of a mouse mammary tumor.
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发表时间：
1992-03
期刊：
影响因子：
11.2
通讯作者：
C. J. Aslakson;F. Miller
中科院分区：
文献类型：
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作者：
C. J. Aslakson;F. Miller
为了确定转移中的选择性步骤，即那些比转移细胞更有效地消除非转移肿瘤细胞的步骤，我们使用单个小鼠乳腺肿瘤的转移亚群(4T1和66Cl4)和非转移亚群(67NR、168FARN和4TO7)，评估了从乳腺脂肪垫中连续传播肿瘤细胞的情况。这些变异亚群中的每一个都对一种或多种选择性药物产生抗药性，因此可以通过在选择性介质中形成菌落来定量鉴定它们。我们发现这两个转移细胞系通过不同的途径转移，而非转移的肿瘤细胞系在不同的扩散点上失败。67NR细胞株未离开原发部位；在实验期间(7周)，在结节、血液和肺中未检测到克隆形成的肿瘤细胞。肿瘤细胞系168FARN是从原发肿瘤转移而来的，因为在整个实验过程中，从引流的淋巴结中培养出克隆形成细胞。然而，由于很少从血液、肺或生命中分离细胞，传播基本上停止在结节。目前尚不清楚168FARN细胞是未能到达这些组织，还是在穿过淋巴结后很快被杀死。4TO7细胞系通过血液扩散，到第19天时一直从肺中恢复，但未能增殖。因此，这个由5个亚群组成的小组确定了肿瘤细胞扩散中不同的选择性失败点，对抗转移治疗的评估应该是有价值的。
To identify selective steps in metastasis, those that eliminate nonmetastatic tumor cells more efficiently than metastatic cells, we have evaluated the sequential dissemination of tumor cells from a mammary fatpad, using both metastatic (4T1 and 66cl4) and nonmetastatic (67NR, 168FARN, and 4TO7) subpopulations of a single mouse mammary tumor. Each of these variant subpopulations is resistant to one or more selective drugs so they could be quantitatively identified by colony formation in selective media. We found that the 2 metastatic cell lines metastasized by different routes and that the nonmetastatic tumor cell lines failed at different points in dissemination. Line 67NR did not leave the primary site; clonogenic tumor cells were not detected in the nodes, blood, or lungs during the experiment (7 weeks). Tumor line 168FARN disseminated from the primary tumor because clonogenic cells were cultured from the draining lymph nodes throughout the experiment. However, dissemination essentially stopped in the node as cells were rarely isolated from blood, lungs, or lives. Whether 168FARN cells failed to reach these tissues or were killed very rapidly after traversing the lymph node is unknown. Line 4TO7 cells disseminated via the blood and were consistently recovered from lungs by day 19 but failed to proliferate. This panel of 5 subpopulations thus identifies different points of selective failure in tumor cell dissemination and should be valuable in the assessment of antimetastatic therapies.