Analysis of mural cell recruitment to tumor vessels

Analysis of mural cell recruitment to tumor vessels
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DOI:
10.1161/hc0102.101437
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发表时间:
2002-01-01
期刊:
影响因子:
37.8
通讯作者:
Betsholtz, C
Betsholtz, C
中科院分区:
医学1区
文献类型:
--
作者:
Abramsson, A;Berlin, Ö;Betsholtz, C

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背景:与正常血管相比,肿瘤血管在结构和功能上都存在异常。壁细胞的有限支持可能导致这些异常。在这里,我们在两种小鼠肿瘤模型中描述了壁细胞募集,并解决了肿瘤血管为什么不能募集适当的壁细胞涂层的问题。方法与结果研究了2种可移植小鼠肿瘤模型(T241纤维肉瘤和KRIB骨肉瘤)的壁细胞向血管的募集。我们发现这两种肿瘤形成了一个血管网络,其壁细胞组织异质性和高度异常。将肿瘤移植到壁细胞中表达lacZ的小鼠体内,表明这些细胞是宿主来源的。尽管肿瘤血管内皮表达PDGF-B(一种壁细胞的胚胎氮),但只有极少数pdgfr - β阳性细胞被发现与正在发育的肿瘤血管有关,这表明可招募的壁细胞有限。我们通过注射T241肿瘤细胞和从表达lacZ的小鼠中分离的胚胎间充质细胞的混合物来检测外源性壁细胞是否可以被募集到肿瘤血管中。在出现的肿瘤中,lacz阳性细胞被有效地招募到肿瘤血管中。结论:t241与KRIB肿瘤血管相关壁细胞组织高度异常。t141肿瘤血管似乎具有很强的招募外源性壁细胞的能力。肿瘤血管稀疏的壁细胞外壳可能是由于可招募的壁细胞有限。
Background-Tumor blood vessels are both structurally and functionally abnormal compared with normal vessels. A limited support of mural cells may contribute to these abnormalities. Here, we characterized mural cell recruitment in 2 mouse tumor models and addressed the question of why tumor vessels fail to recruit a proper coat of mural cells.Methods and Results-We studied mural cell recruitment to the vasculature of 2 transplantable mouse tumor models, T241 fibrosarcoma and KRIB osteosarcoma. We found that both tumors formed a vessel network with heterogeneous and L highly abnormal organization of mural cells. Transplantation of tumors to mice expressing lacZ in mural cells demonstrated that these cells were host-derived. Although tumor vessel endothelium expressed PDGF-B, an embryonic nitrogen for mural cells, only very few PDGFRbeta-positive cells were found to be associated with the developing tumor vasculature, suggesting a limited pool of recruitable mural cells. We tested whether exogenous mural cells could be recruited to tumor vessels by injecting mixtures of T241 tumor cells and embryonic mesenchymal cells isolated from mice expressing lacZ in mural cells. In the tumors that arose, lacZ-positive cells were efficiently recruited to the tumor vessels.Conclusions-T241 and KRIB tumors show a similar highly abnormal organization of vessel-associated mural cells. T241 tumor vessels seem highly capable of recruiting exogenously added mural cells. The sparse mural cell coat of tumor vessels may result from a limited pool of mural cells available for recruitment.