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目的:探讨人乳腺癌细胞增殖与血管生成方式和时间的超微结构特点,明确人乳腺癌生长中VEGF、F8因子表达水平及其意义。方法:应用人乳腺癌细胞系 MCF—7原位移植 SCID鼠,光镜、电镜动态观察肿瘤生长与血管生成的细胞形态。结合免疫组化检测 VEGF、F8因子的表达水平。结果:人乳腺癌细胞系 MCF—7移植后 1、2天生存靠固有组织的血管滋养生长,肿瘤组织中未见新生血管生成。肿瘤生长第3天时,肉眼可见周围血管向移植的肿瘤表面延伸,电镜下观察在存活的癌细胞中可见血管母细胞出现。第6天时,在癌细胞增生活跃区血管母细胞演化为血管内皮细胞。此时癌细胞群与新生的肿瘤微血管紧密相连。微血管邻旁周边可见极少量的蛋白质网架。第8~10天,内皮细胞有较丰富的线粒体,粗面内质网增多,池内含中等量蛋白质,血管内皮的腔面小球增多,光镜下可见肿瘤周围的血管与肿瘤新生血管相通。VEGF、F8因子的表达与肿瘤增殖、侵袭、新生血管生成有关。结论:移植初期人乳腺癌细胞可分泌血管生成因子。肿瘤周围的血管母细胞被激活。快速增殖期癌细胞可诱导血管内皮细胞增生形成肿瘤新生血管。逐步演化的肿瘤新生血管与肿瘤边缘固有的血管相连通。
OBJECTIVE: To investigate the ultrastructural features of human breast cancer cell proliferation and angiogenesis patterns and time, to clarify the expression of VEGF and F8 in human breast cancer and its significance. Methods: SCID mice were implanted in situ with human breast cancer cell line MCF-7. The cell morphology of tumor growth and angiogenesis was observed by light microscope and electron microscope. Combined with immunohistochemistry, the expression of VEGF and F8 were detected. Results: The human breast cancer cell line MCF-7 was nourished and grew on the 1,2-day after transplantation, and no neovascularization was found in the tumor tissue. On the third day of tumor growth, peripheral blood vessels were visible to the surface of the transplanted tumor by naked eyes. The appearance of vascular cells appeared in the surviving cancer cells under the electron microscope. On day 6, the vascular blast cells evolved into vascular endothelial cells in the proliferative active area of cancer cells. At this time, the cancer cell population is closely connected with the neoplasm of tumor microvessels. Near the microvascular adjacent to a very small amount of protein network can be seen. From the 8th to the 10th day, endothelial cells were enriched in mitochondria, increased in rough endoplasmic reticulum, with moderate amount of protein in the pool and increased luminal surface of the vascular endothelium. The light-microscope showed that the blood vessels around the tumor and tumor neovascularization were connected. The expression of VEGF and F8 are related to tumor proliferation, invasion and neovascularization. Conclusion: Human breast cancer cells can secrete angiogenic factors during the early stage of transplantation. Vascular blast cells around the tumor are activated. Rapid proliferation of cancer cells can induce endothelial cell proliferation to form tumor neovascularization. The evolving tumor neovasculature communicates with the inherent blood vessels at the periphery of the tumor.