Evaluation of metastatic and angiogenic potentials of human colon carcinoma cells in chick embryo model systems.

Evaluation of metastatic and angiogenic potentials of human colon carcinoma cells in chick embryo model systems.
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DOI:
10.1007/s10585-009-9293-4
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发表时间:
2009
影响因子:
4
通讯作者:
Deryugina, Elena I.
Deryugina, Elena I.
中科院分区:
医学3区
文献类型:
--
作者:
Subauste, M. Cecilia;Kupriyanova, Tatyana A.;Conn, Erin M.;Ardi, Veronica C.;Quigley, James P.;Deryugina, Elena I.

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通过比较体内高转移性结肠癌细胞系SW 620与其同基因的非转移性SW 480细胞变体,在独立的鸡胚模型中验证了侵袭性人结肠癌细胞的转移和血管生成潜能增加。在实验转移模型中,两种类型的细胞在绒毛尿囊膜(CAM)血管中迅速停滞,如定量PCR和免疫组织化学所示。活细胞成像还表明,SW 620和SW 480细胞都有效地从CAM毛细血管系统外渗。但24-48 h后CAM组织中仅出现少量SW 480细胞。相反,SW 620细胞的数量呈指数增加,表明转移性结肠癌细胞在体内的增殖和存活优势。在CAM血管附近发现多细胞SW 620病灶。结肠癌SW 620细胞的转移能力增加和VEGF表达之间的正相关性通过抗VEGF治疗对转移定植水平和邻近肿瘤细胞灶的血管密度的实质性抑制作用来证明。此外,鸡胚血管生成模型证实了高水平的VEGF依赖的血管生成诱导的SW 620细胞,但不是SW 480细胞。因此,鸡胚实验转移和CAM血管生成模型似乎协调地反映了晚期结肠癌的关键特征,即,获得提高的存活率和增加的血管生成潜力,两者都构成结肠癌进展的关键决定因素。使用快速和定量的鸡胚模型可能会提供替代方法,以传统的哺乳动物模型系统筛选抗癌药物。
Increased metastatic and angiogenic potentials of aggressive human colon carcinoma cells were verified in independent chick embryo models by comparing in vivo highly metastatic SW620 colon carcinoma cell line with its isogenic, non-metastatic SW480 cell variant. In the experimental metastasis model, both cell types rapidly arrested in the chorioallantoic membrane (CAM) vasculature as demonstrated by quantitative PCR and immunohistochemistry. Live cell imaging also indicated that both SW620 and SW480 cells efficiently extravasated from the CAM capillary system. However, only few SW480 cells were present in the CAM tissue after 24–48 h. In contrast, the numbers of SW620 cells increased exponentially, indicating proliferative and survival advantages of metastatic colon carcinoma cells in vivo. Multicellular SW620 foci were identified in close proximity to CAM blood vessels. A positive correlation between increased metastatic ability and VEGF-expression of colon carcinoma SW620 cells was demonstrated by the substantial inhibitory effects of anti-VEGF treatment on the levels of metastatic colonization and density of blood vessels adjacent to tumor cell foci. Furthermore, the chick embryo angiogenesis model confirmed high levels of VEGF-dependent angiogenesis induced by SW620 cells, but not SW480 cells. Thus, chick embryo experimental metastasis and CAM angiogenesis models appear to coordinately reflect critical features of advanced colon carcinomas, i.e., the acquisition of enhanced survival and increased angiogenic potentials, both constituting critical determinants of colon cancer progression. The use of rapid and quantitative chick embryo models might provide alternative approaches to conventional mammalian model systems for screening anti-cancer agents.
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