Tumor dormancy in vivo by prevention of neovascularization.
Tumor dormancy in vivo by prevention of neovascularization.
复制标题
通过预防新血管形成，体内肿瘤休眠。
DOI：
10.1084/jem.136.2.261
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发表时间：
1972-08-01
影响因子：
15.3
通讯作者：
Folkman, J
中科院分区：
文献类型：
--
作者：
Gimbrone, M A Jr;Leapman, S B;Cotran, R S;Folkman, J
休眠实体瘤是通过防止新生血管在体内产生的。将小块间变性布朗-皮尔斯癌直接植入易感家兔的虹膜上，它们总是血管化的。观察到一种特征性的生长模式，包括血管前期、血管期和晚期，并在2周内以眼睛的破坏而终止。通过静脉注射荧光素灌注和组织学切片证实，指数体积增加的开始与植入物的血管化相吻合。相比之下，植入物放置在前房，离虹膜有一段距离，没有血管化。在最初生长成球体后，它们保持在与血管前虹膜植入物相当的小尺寸，持续时间长达6周。虽然在扩张方面处于休眠状态，但这些无血管肿瘤含有大量活的和有丝分裂活跃的肿瘤细胞。当移植到虹膜上时，血管形成之后是快速的侵入性生长。这些观察结果提示新生血管是实体瘤恶性生长的必要条件。当一小部分肿瘤细胞不能从周围的宿主组织中诱导新的血管生长时，就会导致群体休眠。这些数据表明，特异性阻断肿瘤诱导的血管生成可能是控制肿瘤生长的有效手段。
Dormant solid tumors were produced in vivo by prevention of neovascularization. When small fragments of anaplastic Brown-Pearce carcinoma were implanted directly on the iris in susceptible rabbits, they always vascularized. A characteristic growth pattern, consisting of prevascular, vascular, and late phases, was observed, which terminated with destruction of the eye within 2 wk. The beginning of exponential volume increase was shown to coincide with vascularization of the implant, as demonstrated by perfusion with intravenous fluorescein and by histologic sections. In contrast, implants placed in the anterior chamber, at a distance from the iris, did not become vascularized. After initial growth into spheroids, they remained arrested at a small size comparable to prevascular iris implants, for periods as long as 6 wk. Although dormant in terms of expansion, these avascular tumors contained a population of viable and mitotically active tumor cells. When reimplanted on the iris, vascularization was followed by rapid, invasive growth. These observations suggest that neovascularization is a necessary condition for malignant growth of a solid tumor. When a small mass of tumor cells is prevented from eliciting new vessel ingrowth from surrounding host tissues, population dormancy results. These data suggest that the specific blockade of tumor-induced angiogenesis may be an effective means of controlling neoplastic growth.