Evaluation of biological characteristics in tumor vessels and clinical application of antagonistic agent for neovascularization

近年来，有研究报道，某种致癌启动子具有血管生成活性，而类视黄醛和维生素D3衍生物则通过抑制血管生成来抑制肿瘤的发生。这些报道提示血管生成可能在癌变过程中起重要作用。在临床环境中，血管生成是肿瘤生长和转移的关键。因此，我们研究以下内容。目的：1)以结肠癌细胞、结肠癌向肝转移细胞和人肝癌细胞为研究对象，探讨血管生成因子与血管内皮（EA-HY 926）增殖活性的关系，明确tnf - α是否能够抑制血管生成；2)研究人肝癌细胞系PLC/PRF/5 （Alexander）细胞的血管生成活性。结果与结论1)结肠癌细胞和转移细胞的平均增殖活性分别为l42%和l52%。虽然不排除存在其他因素的可能性，但结肠癌细胞在原发癌细胞中产生VEGF，在转移细胞中产生bFGF等血管生成因子。tnf - α对抑制血管生成无效。2)扩散室实验表明，Alexander细胞促进新生血管生成，内皮细胞中Ets- 1呈阳性。提示肝细胞癌具有较强的血管生成增殖活性，而Ets- 1可能在血管生成中起重要作用。

BackgroundRecently, it has been reported that a certain carcinogenetic promoter has an angiogenetic activity while retinoid and derivatives from vitamin D3 inhibit carcinogenesis thorough depression of angiogenesis. These reports indicate that angiogenesis may play an important role on carcinogenesis. In clinical settings, angiogenesis is crucial for tumor growth and metastasis. Thus, we investigate the following.Aims1) to examine relationship between angiogenetic factors and proliferative activity for vascular endothelium (EA-HY 926) using colon cancer cells, metastastatic cells of colon cancer to liver, and cells of human hepatocellular carcinoma, and to clarify whether TNT-alpha is able to inhibit angiogenesis or not2) to investigate the angiogenetic activity of PLC/PRF/5 (Alexander) cells, which is a human hepatoma cell line, with diffusion chamber assay using E 26 transformation-specific-1 (Ets-1)Results and Conclusion1) Mean proliferative activity of colon cancer cells and metastasized cells was l42 %, and l52 %, respectively. Although it was not ruled out of the possibility that there were other factors, colon cancer cells produced angiogenetic factors such as VEGF in original cancer cells and bFGF in the metastasized cells. TNF-alpha was not effective on inhibition of angiogenesis.2) Alexander cells accelerate angiogenesis in diffusion chamber assay and Ets- 1 was positive in the endothelium of the new vessels. These results suggest that hepatocellular carcinoma has strong proliferative activity for angiogenesis and Ets- 1 may play an important role on angiogenesis.