Alterman A L, Stackpole C W
Department of Pathology, New York Medical College, Valhalla 10595.
Clin Exp Metastasis. 1989 Jan-Feb;7(1):15-23. doi: 10.1007/BF02057178.
Subcutaneous tumors initiated with mouse B16 melanoma clones G3.5 and G3.12 disseminated visible spontaneous brain metastases in 67 per cent and 32 per cent, respectively, of mice with extensive lung metastasis. Most brain metastases appeared as pigmented emboli within blood vessels of the leptomeninges overlying the cerebral cortex. Intravascular metastases consisted of tumor cell aggregates surrounded by fibrous material and generally contained viable cells that proliferated in culture. Some metastatic emboli apparently proliferated intravascularly to such an extent as to cause vessel disruption, permitting tumor invasion into the adjacent cerebral cortex. Cultured cells from G3.12 leptomenings metastases produced tumors that metastasized to a much greater extent than unselected G3.12 tumors, but brain metastasis still occurred only secondarily, after initial dissemination to the lungs. In contrast, G3.5 brain metastasis-derived populations formed tumors that ultimately metastasized to the brain to lesser extents than did unselected G3.5 tumors. One selected variant, G3.12/BM2, reproducibly formed visible and viable brain metastases in more than 80 per cent of tumor-bearing mice, and lethal or potentially lethal brain metastases in 10-15 per cent of mice. This variant may serve as a model for clinical brain metastasis.
用小鼠B16黑色素瘤克隆G3.5和G3.12引发的皮下肿瘤，在出现广泛肺转移的小鼠中，分别有67%和32%出现了可见的自发性脑转移。大多数脑转移表现为覆盖大脑皮层的软脑膜血管内的色素性栓子。血管内转移由被纤维物质包围的肿瘤细胞聚集体组成，通常含有在培养中增殖的活细胞。一些转移性栓子显然在血管内增殖到足以导致血管破裂的程度，从而使肿瘤侵入相邻的大脑皮层。来自G3.12软脑膜转移灶的培养细胞产生的肿瘤，其转移程度比未筛选的G3.12肿瘤大得多，但脑转移仍然只是在最初扩散到肺部之后才继发发生。相比之下，G3.5脑转移衍生群体形成的肿瘤，最终转移到大脑的程度比未筛选的G3.5肿瘤小。一个筛选出的变体G3.12/BM2，在超过80%的荷瘤小鼠中可重复地形成可见且存活 的脑转移灶，在10%-15%的小鼠中形成致死性或潜在致死性脑转移灶。这个变体可作为临床脑转移的一个模型。
