Funahashi Y, Wakabayashi T, Semba T, Sonoda J, Kitoh K, Yoshimatsu K
Cancer Research Unit, Tsukuba Research Laboratories, Eisai Co. Ltd., Ibaraki, Japan.
Oncol Res. 1999;11(7):319-29.
We have developed an improved mouse dorsal air sac model for quantifying in vivo tumor-induced angiogenesis. In our improved model, tumor angiogenesis is determined by measuring the blood volume in an area of skin held in contact with a tumor cell-containing chamber, using 51Cr-labeled red blood cells (RBC). The blood volume induced by murine B16-BL6 melanoma cells increased linearly with the cell number in the range from 2 x 10(5) to 5 x 10(6). Ten of 11 human tumor cell lines examined induced a significant increment in blood volume. For three representative human tumor cell lines (A549, WiDr. and HT1080 cells) that showed different angiogenic potencies, the levels of vascular endothelial growth factor (VEGF) produced by the tumor cells cultured under conditions of hypoxia and high cell density were correlated with the degree of in vivo angiogenesis. Using the improved model, it was confirmed that TNP-470, a well-known inhibitor, and borrelidin, an antibiotic from Streptomyces rochei, significantly inhibited the WiDr cell-induced angiogenesis. Borrelidin also inhibited spontaneous lung metastasis of B16-BL6 melanoma at the same dose that inhibited angiogenesis. Our results suggest that the improved mouse dorsal air sac model can be used for simple and quantitative measurement of tumor-induced angiogenesis and its inhibition.
我们已经开发出一种改进的小鼠背部气囊模型，用于定量体内肿瘤诱导的血管生成。在我们改进的模型中，肿瘤血管生成是通过使用51Cr标记的红细胞（RBC）测量与含肿瘤细胞腔室接触的皮肤区域中的血容量来确定的。小鼠B16 - BL6黑色素瘤细胞诱导的血容量在2×10（5）至5×10（6）的细胞数量范围内与细胞数量呈线性增加。所检测的11种人类肿瘤细胞系中有10种诱导血容量显著增加。对于三种显示出不同血管生成能力的代表性人类肿瘤细胞系（A549、WiDr和HT1080细胞），在缺氧和高细胞密度条件下培养的肿瘤细胞产生的血管内皮生长因子（VEGF）水平与体内血管生成程度相关。使用改进的模型，证实了著名的抑制剂TNP - 470和来自罗氏链霉菌的抗生素博莱霉素显著抑制WiDr细胞诱导的血管生成。博莱霉素在抑制血管生成的相同剂量下也抑制了B16 - BL6黑色素瘤的自发性肺转移。我们的结果表明，改进的小鼠背部气囊模型可用于简单定量测量肿瘤诱导的血管生成及其抑制作用。
