Mosaic blood vessels in tumors: Frequency of cancer cells in contact with flowing blood

Mosaic blood vessels in tumors: Frequency of cancer cells in contact with flowing blood
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DOI:
10.1073/pnas.97.26.14608
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发表时间:
2000-12-19
影响因子:
11.1
通讯作者:
Munn, LL
Munn, LL
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Chang, YS;di Tomaso, E;Munn, LL

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血管内皮细胞和肿瘤细胞构成管腔表面的“马赛克”血管的存在对转移、药物输送和抗血管治疗具有深远的意义。然而,人们对肿瘤中镶嵌血管的频率和重要性知之甚少。用CD31和CD105鉴定内皮细胞和肿瘤细胞的内源性绿色荧光蛋白标记,我们发现,在小鼠结肠癌两个不同部位移植的骨盆血管中,约有15%是马赛克血管,焦点区域未检测到CD31/CD105免疫反应,肿瘤细胞似乎与管腔接触。在这些结肠癌中,这些区域约占镶嵌血管周长的25%,或约占总血管表面积的4%。此外,我们在人类结肠癌活检组织中发现了类似数量的马赛克血管。我们的结果与观察到的每克肿瘤每天大约有10(6)个细胞脱落是一致的。更重要的是,我们的数据为细胞毒剂的抗血管作用提供了一个可能的解释,并提出了针对肿瘤血管系统的潜在策略。
The presence of "mosaic" vessels in which both endothelial cells and tumor cells form the luminal surface has profound implications for metastasis, drug delivery, and antivascular therapy. Yet little is known of the frequency, and thus importance, of mosaic vessels in tumors. Using CD31 and CD105 to identify endothelial cells and endogenous green fluorescent protein labeling of tumor cells, we show that approximate to 15% of pelf used vessels of a colon carcinoma xenografted at two different sites in mice were mosaic vessels having focal regions where no CD31/CD105 immunoreactivity was detected and tumor cells appeared to contact the Vessel lumen. These regions occupied approximate to 25% of the perimeter of the mosaic vessels, or approximate to4% of the total vascular surface area in these colon carcinomas. In addition, we found similar numbers of mosaic vessels in human colon carcinoma biopsies. Our results are consistent with the observation that approximate to 10(6) cells are shed daily per g of tumor. More importantly, our data offer a possible explanation for the antivascular effects of cytotoxic agents and suggest potential strategies for targeting the tumor vasculature.