Grunt T W, Lametschwandtner A, Karrer K, Staindl O
Scan Electron Microsc. 1986(Pt 2):557-73.
53 Lewis lung carcinomas implanted subcutaneously into C57BL/6-mice were examined. The animals were killed at various stages of tumor growth (TG) and prepared for histology and for scanning electron microscopy (critical-point-dried tissue; vascular corrosion casts). Prior to casting animals were rinsed using different perfusion pressures. Casting was done by manual injection of the resin, whereby different influx-rates were applied resulting in low, medium and high pressure preparations. We discern 3 phases of tumor angiogenesis (TA) occurring during 4 stages of TG among which vasodilation establishes the first reaction of the host vascular system to a growing tumor implant. During this stage 1 of TG, tumor nidation, nearby sinusoidal dilated host capillaries form globular outgrowings (phase 1 of TA). Subsequently radially arranged sprouts, which preferentially arise from venous host vessels, grow into the centre of the implant (phase 2 of TA). Stage 2 of TG, early tumor growth, is characterized by necrosis of the central tumor tissue and the development of a central avascular cavity. Thus the tumor vascular system is organized like a hollow sphere with a central cavity and a peripheral vascular "envelope" with large vessels embracing the tumor and centrifugally growing vascular sprouts, which arise from the venous part of the vascular "envelope" and invade the surrounding host tissue (phase 3 of TA). During stage 3 of TG, late tumor growth, many vessels of the basket-like vascular "envelope" obliterate. In stage 4 of TG, prefinal phase, the peripheral vascular density decreases continuously. Thus vascular sprouting and proliferation of viable tumor cells is confined to basal regions of the tumor.
对皮下植入C57BL/6小鼠体内的53个Lewis肺癌进行了检查。在肿瘤生长(TG)的不同阶段处死动物,并制备用于组织学和扫描电子显微镜检查的样本(临界点干燥组织;血管铸型)。在铸型前,使用不同的灌注压力冲洗动物。通过手动注射树脂进行铸型,采用不同的流入速率,从而得到低压、中压和高压制剂。我们识别出在TG的4个阶段中发生的肿瘤血管生成(TA)的3个阶段,其中血管舒张是宿主血管系统对生长中的肿瘤植入物的第一反应。在TG的这个第1阶段,即肿瘤着床阶段,附近扩张的窦状宿主毛细血管形成球状突出物(TA的第1阶段)。随后,主要从静脉宿主血管产生的呈放射状排列的芽生,生长到植入物中心(TA的第2阶段)。TG的第2阶段,即肿瘤早期生长阶段,其特征是中央肿瘤组织坏死和中央无血管腔的形成。因此,肿瘤血管系统组织成一个空心球体,有一个中央腔和一个外周血管“包膜”,大血管围绕肿瘤,血管芽生从血管“包膜”的静脉部分离心生长并侵入周围宿主组织(TA的第3阶段)。在TG的第3阶段,即肿瘤晚期生长阶段,篮状血管“包膜”的许多血管闭塞。在TG的第4阶段,即终末前期,外周血管密度持续降低。因此,血管芽生和存活肿瘤细胞的增殖局限于肿瘤的基底部区域。