Bone marrow-derived lin-c-kit+Sca-1+ stem cells do not contribute to vasculogenesis in Lewis lung carcinoma
Bone marrow-derived lin-c-kit+Sca-1+ stem cells do not contribute to vasculogenesis in Lewis lung carcinoma
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DOI：
10.1593/neo.04523
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发表时间：
2005-03-01
期刊：
影响因子：
4.8
通讯作者：
Weissleder, R
中科院分区：
文献类型：
--
作者：
Patil, VRS;Friedrich, EB;Weissleder, R
肿瘤脉管系统的发育被认为是通过两个互补的过程发生的：从宿主预先存在的血管中萌芽血管生成，以及血管生成，其中涉及通过循环内皮细胞（EC）、内皮祖细胞（EPC）或潜在骨髓衍生细胞的特异性募集、分化和血管掺入来自发发育血管。然而，最近的报告对骨髓来源的细胞有助于肿瘤新生血管形成的观点提出了挑战，声称其在肿瘤血管发育中发挥着独特的发芽血管生成作用。在本研究中，我们探讨了在同基因骨髓移植模型中皮下植入Lewis肺癌中骨髓来源的lin(-)c-kit(+)Sca-1(+)干细胞的募集行为。我们观察到，尽管 lin(-)c-kit(+)Sca-1(+) 及其衍生细胞在体内表现出对癌症的显着募集，但它们似乎对肿瘤新生血管形成没有功能性贡献。此外，我们的结果支持这样的假设：癌症中的新血管形成主要是通过邻近和先前存在的脉管系统的内皮化而发生的。
The development of tumor vasculature is thought to occur through two complementary processes: sprouting angiogenesis from preexisting blood vessels of the host, and vasculogenesis, which involves the spontaneous development of vessels through specific recruitment, differentiation, and vascular incorporation of circulating endothelial cells (EC), endothelial progenitor cells (EPC), or potentially bone marrow-derived cells. Recent reports, however, have challenged the belief that bone marrow-derived cells contribute to tumor neovascularization, claiming an exclusive role for sprouting angiogenesis in tumor blood vessel development. In the present study, we explored the recruitment behavior of bone marrow-derived lin(-)c-kit(+)Sca-1(+) stem cells to subcutaneously implanted Lewis lung carcinoma in a syngeneic bone marrow transplantation model. We observed that although lin(-)c-kit(+)Sca-1(+) and their derived cells demonstrate significant recruitment to carcinomas in vivo, they do not appear to functionally contribute to tumor neovascularization. Furthermore, our results support the hypothesis that new vessel formation in carcinomas occurs primarily through endothelialization from adjacent and preexisting vasculature.