【作者】 张诗武； 孙保存； 张丹芳； 郭华； 赵秀兰；

【Author】 Baocun Sun Shiwu Zhang Zhang Danfang Hua Guo Xiulan Zhao

【机构】 天津医科大学附属肿瘤医院肿瘤研究所；

【摘要】 目的:研究黑色素瘤细胞是否存在线形程序性坏死,明确线形程序性坏死与肿瘤血管生成拟态之间的关系。方法:雌雄各半的60只C57纯系小鼠分成12组,每组5只, 适应1周后将黑色素瘤单细胞悬液B16接种到60只C57纯系小鼠体内。10天后在移植瘤体积大小约为0．2cm时连续 12天每天处死一组动物,留取处死动物部分新鲜肿瘤组织标本经戊二醛固定后电镜下观察,剩余肿瘤标本制作成石蜡切片,在切片上进行脱氧核糖核酸末端转移酶介导的dUTP缺口末端标记(TUNEL)染色和caspase-3、Bax免疫组织化学染色观察细胞线形程序性坏死与肿瘤血液供应间的关系。结果:在黑色素移植瘤生长早期,部分肿瘤细胞出现线形程序性坏死,坏死后形成的组织裂隙和机体内皮依赖性血管相通即可成为肿瘤血液供应的暂时性通道,即血管生成拟态; 随着肿瘤体积的不断增加,程序性坏死产生的暂时性血液通道内壁逐渐被增生的血管内皮细胞对覆,线形程序性坏死形成的血管生成拟态、马赛克血管(血管生成拟态和内皮依赖性血管之间的过度形式)和内皮依赖性血管是存在于黑色素瘤组织内不同的血液供应模式。结论:黑色素瘤是一种高度恶性肿瘤,肿瘤细胞分化较低,肿瘤细胞内存在胚胎样基因型。在肿瘤组织快速生长早期,在肿瘤自身凋亡调控基因作用下,伴以缺血缺氧等周围环境的刺激,部分肿瘤细胞发生线形程序性坏死,程序性坏死产生的裂隙与内皮依赖性血管相通可以满足肿瘤组织对血液供应的需要。更多还原

【Abstract】 Objective: To investigate the possibility that line-shaped programmed necrosis of tumor cells establish the spatial foundation of vasculogenic mimicry and reveal the relationship between line-shaped programmed necrosis, vasculogenic mimicry, mosaic vessels and endot-helium-dependent vessels. Methods: Sixty C57 mice males and females of equal numbers were divided into twelve groups and every group has five mice. Melanoma cells B16 were inoculated into groins of the mice. These mice were consecutively sacrificed one group per day when the diameter of the engrafted tumor was about 1-2 micrometers and 11 days after inoculation. We used immunohistochemi-cal analyses, TUNEL stain and electron microscope to identify the relationship of line-shaped programmed necrosis and tumor blood supply. Results: In the early stage of melanoma rapid growth, some tumor cells appear line-shaped programmed necrosis to form some channels. The spatial foundation made by programmed necrosis connecting with extra-cellular matrix remold is the basis of vasculogenic mimicry forming. At last, vasculogenic mimicry was gradually substituted by mosaic vessels and en-dothelium-dependent vessels in the procession of tumor growth. Conclusion: Melanoma is a high-grade malignant tumor and the tumor cells are dedifferentiated with embryonic-like gene type. In the rapid growth stage, the blood supply from endothelium-dependent vessels can not satisfy the need of the tumor and line-shaped programmed necrosis appear in tumor mass under the regulation of programmed necrosis-associated genes and the stimulation from the hypoxia surround. Channels produced though programmed necrosis can canalize with endothelium-dependent vessels and satisfy the need of the tumor cells.更多还原