Identification and characterization of the blood vessels of solid tumors that are leaky to circulating macromolecules.
Identification and characterization of the blood vessels of solid tumors that are leaky to circulating macromolecules.
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发表时间：
1988-10
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通讯作者：
H. Dvorak;J. Nagy;J. Dvorak;A. Dvorak
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作者：
H. Dvorak;J. Nagy;J. Dvorak;A. Dvorak
肿瘤微血管对血浆蛋白具有高渗透性，但具体渗漏的血管尚未确定。为了研究这个问题，我们用荧光显微镜、光镜和电子显微镜研究了不同大小的循环示踪剂在实体可移植癌动物体内的外渗情况。在所有研究的5个肿瘤中，70和150 kD荧光(FITC)-葡聚糖和胶体碳从单个肿瘤结节周围和肿瘤-宿主界面诱导的突出血管丛中大量泄漏。渗漏血管为成熟的静脉或小静脉，内衬连续的内皮；大多数内皮细胞间连接闭合。未成熟的界面血管和肿瘤穿透血管未明显泄漏这些大分子示踪剂。3 kD的fitc -葡聚糖从位于肿瘤周围的静脉或小静脉渗漏，但也从肿瘤穿透血管和供应正常组织的毛细血管外渗。这些数据与肿瘤血管的功能和解剖异质性相关，并为实体肿瘤中循环分子（如单克隆抗体和杀瘤药物）的分布提供了理论依据。
The tumor microvasculature is hyperpermeable to plasma proteins, but the specific vessels that leak have not been identified. To investigate this question, the extravasation of circulating tracers of varying size was studied by fluorescence, light, and electron microscopy in animals bearing solid transplantable carcinomas. In all five tumors studied, 70 and 150 kD fluoresceinated (FITC)-dextrans and colloidal carbon leaked extensively from the prominent vascular plexus that was induced around individual tumor nodules and at the tumor-host interface. Leaky vessels were mature veins or venules, lined by a continuous endothelium; most had closed interendothelial cell junctions. Immature interface vessels and tumor-penetrating vessels did not leak these macromolecular tracers significantly. Three kD of FITC-dextran leaked from peripherally situated tumor veins or venules but also extravasated from tumor-penetrating vessels and capillaries supplying normal tissues. These data correlate the functional and anatomic heterogeneity of tumor vessels and provide a rationale for the distribution of circulating molecules such as monoclonal antibodies and tumoricidal drugs in solid tumors.