DORMANCY OF MICROMETASTASES - BALANCED PROLIFERATION AND APOPTOSIS IN THE PRESENCE OF ANGIOGENESIS SUPPRESSION
DORMANCY OF MICROMETASTASES - BALANCED PROLIFERATION AND APOPTOSIS IN THE PRESENCE OF ANGIOGENESIS SUPPRESSION
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DOI：
10.1038/nm0295-149
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发表时间：
1995-02-01
期刊：
影响因子：
82.9
通讯作者：
FOLKMAN, J
中科院分区：
文献类型：
--
作者：
HOLMGREN, L;OREILLY, MS;FOLKMAN, J
在癌症患者中，潜伏的微转移通常是无症状的，临床上检测不到，持续数月或数年，直到复发。我们研究了小鼠在血管生成抑制下的潜伏性肺转移。去除对血管生成的抑制后，转移瘤生长迅速。通过溴脱氧尿嘧啶核苷掺入和免疫组织化学染色增殖细胞核抗原检测的肿瘤细胞增殖，在潜伏期和成长期转移瘤中没有显著差异。然而，潜伏期转移的肿瘤细胞的凋亡率要高出三倍以上。这些数据表明，当肿瘤细胞的增殖与相当的细胞死亡率相平衡时，转移仍然处于休眠状态，这表明血管生成抑制剂通过间接增加肿瘤细胞的凋亡来控制转移生长。
In cancer patients, dormant micrometastases are often asymptomatic and clinically undetectable, for months or years, until relapse. We have studied dormant lung metastases under angiogenesis suppression in mice. The metastases exhibited rapid growth when the inhibition of angiogenesis was removed. Tumour cell proliferation, as measured by bromodeoxyuridine incorporation and immunohistochemical staining proliferating cell nuclear antigen, was not significantly different in dormant and growing metastases. However, tumour cells of dormant metastases exhibited a more than threefold higher incidence of apoptosis. These data show that metastases remain dormant when tumour cell proliferation is balanced by an equivalent rate of cell death and suggest that angiogenesis inhibitors control metastatic growth by indirectly increasing apoptosis in tumour cells.