The seed and soil hypothesis: vascularisation and brain metastases
The seed and soil hypothesis: vascularisation and brain metastases
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DOI：
10.1016/s1470-2045(01)00622-2
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发表时间：
2002-01-01
期刊：
影响因子：
51.1
通讯作者：
Bucana, CD
中科院分区：
文献类型：
--
作者：
Fidler, IJ;Yano, S;Bucana, CD
建立与脑转移瘤生长相关的小鼠模型，对脑转移瘤的生物学和治疗研究具有重要意义。将人类肿瘤细胞注射到同基因或裸鼠的颈内动脉中，会在大脑的特定区域产生实验性转移；这不是由于最初细胞停滞、移动或侵袭的模式，而是由于转移的肿瘤细胞生长的能力。脑转移瘤的进行性增长是否依赖于新生血管尚不清楚。免疫组织化学和形态计量学分析表明，裸鼠实验性脑转移瘤内的血管密度，或来自人类肺癌的脑转移瘤内的血管密度，低于邻近的无肿瘤脑实质。然而，与脑转移相关的血管扩张，并含有许多分裂的内皮细胞。免疫组织化学分析还显示，距离血管小于100微米的肿瘤细胞是存活的，而距离更远的肿瘤细胞经历了凋亡。血脑屏障在直径小于0.25 mm的实验性脑转移瘤中及其周围是完整的，但在较大的转移瘤中是漏水的。然而，这些皮损对化疗药物具有抗药性。大脑微环境是如何影响肿瘤细胞的生物学行为的，这是一个深入研究的主题。
The development of a relevant mouse model for the establishment and growth of brain metastases is essential for study of the biology and therapy of brain metastasis. Injection of human tumour cells into the internal carotid artery of syngeneic or nude mice produces experimental metastases in specific regions of the brain; these are not due to patterns of initial cell arrest, motility, or invasiveness, but rather to the ability of metastatic tumour cells to grow. Whether the progressive growth of brain metastases depends on neovascularisation is not clear. Immunohistochemical and morphometric analyses show that the density of blood vessels within experimental metastases in the brains of nude mice, or within brain metastases derived from human lung cancer, is lower than in the adjacent, tumour-free brain parenchyma. However, blood vessels associated with brain metastases are dilated and contain many dividing endothelial cells. Immunohistochemical analysis also reveals that tumour cells located less than 100 mum from a blood vessel are viable, whereas more distant tumour cells undergo apoptosis. The blood-brain barrier is intact in and around experimental brain metastases smaller than 0.25 mm in diameter, but is leaky in larger metastases. Nevertheless, the lesions are resistant to chemotherapeutic drugs. The way in which the brain microenvironment influences the biological behaviour of tumour cells is a subject of intense investigation.