Vascular Biology, Hokkaido University Graduate School of Dental Medicine, N13 W7, Kita-ku, Sapporo 060-8586, Japan.
Biochem Biophys Res Commun. 2010 Apr 16;394(4):947-54. doi: 10.1016/j.bbrc.2010.03.089. Epub 2010 Mar 17.
Tumor angiogenesis is necessary for solid tumor progression and metastasis. Increasing evidence indicates that tumor endothelial cells (TECs) are more relevant to the study of tumor angiogenesis than normal endothelial cells (NECs) because their morphologies and gene expression are different from NECs. However, it is challenging to isolate and culture large numbers of pure ECs from tumor tissue since the percentage of ECs is only about 1-2% and tumor cells and fibroblasts easily overgrow them. In addition, there has been concern that isolated TECs may lose their special phenotype once they are dissociated from tumor cells. In this study, we have successfully purified murine TECs from four different human tumor xenografts and NECs from murine dermal tissue. Isolated ECs expressed endothelial markers, such as CD31, VE-cadherin (CD144), and endoglin (CD105), for more than 3 months after isolation. TECs maintained tumor endothelial-specific markers, such as tumor endothelial marker 8 (TEM8) and aminopeptidase N (APN), as in tumor blood vessels in vivo. In addition, TECs were more proliferative and motile than NECs. TECs showed a higher response to VEGF and higher expression of VEGF receptors-1 and -2 than NECs did. Stem cell antigen-1 was up-regulated in all four TECs, suggesting that they have a kind of stemness. Cultured TECs maintain distinct biological differences from NECs as in vivo. In conclusion, it was suggested that TECs are relevant material for tumor angiogenesis research.
肿瘤血管生成对于实体瘤的进展和转移是必要的。越来越多的证据表明，肿瘤内皮细胞（TECs）比正常内皮细胞（NECs）更能反映肿瘤血管生成的研究，因为它们的形态和基因表达与 NECs 不同。然而，由于 ECs 的比例仅约为 1-2%，并且肿瘤细胞和成纤维细胞容易过度生长，因此从肿瘤组织中分离和培养大量的纯 ECs 具有挑战性。此外，人们一直担心分离的 TECs 一旦与肿瘤细胞分离，可能会失去其特殊表型。在这项研究中，我们已经成功地从四种不同的人源肿瘤异种移植中纯化了小鼠 TECs 和从鼠真皮组织中纯化了 NECs。分离的 ECs 在分离后超过 3 个月表达内皮标记物，如 CD31、VE-钙黏蛋白（CD144）和内胚层蛋白（CD105）。TECs 保持了肿瘤内皮特异性标记物，如肿瘤内皮标记物 8（TEM8）和氨肽酶 N（APN），与体内肿瘤血管中的标记物相同。此外，TECs 的增殖和迁移能力比 NECs 更强。TECs 对 VEGF 的反应更高，并且表达更高水平的 VEGF 受体-1 和 -2。所有四种 TECs 中的干细胞抗原-1 均上调，表明它们具有某种干性。培养的 TECs 保持与体内不同的独特生物学差异。总之，提示 TECs 是肿瘤血管生成研究的相关材料。
