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首页> 外文期刊>Cell cycle >Vascular integration of endothelial progenitors during multistep tumor progression.
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Vascular integration of endothelial progenitors during multistep tumor progression.

机译：在多步肿瘤进展过程中内皮祖细胞的血管整合。

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摘要

Bone marrow-derived endothelial precursor cells contribute to tumor neovascularization. However, it is unclear when during progressive tumor growth circulating precursors are recruited into the preexisting vascular network, and how they home specifically into the tumor microenvironment. Here, we summarize recent findings from mouse models of multistage carcinogenesis, which reveal distinct phases of angiogenic activity. Only advanced tumors with a highly heterogeneous, sprouting vasculature recruite endothelial progenitors into neovessels. Surprisingly, during progressive tumor growth endothelial cells acquire new characteristics and secrete CC chemokines, a group of chemoattractants with adjacent cysteins, which play a dual role by enhancing neovascularization in an autocrine and endocrine fashion. Locally, chemokines stimulate endothelial proliferation; systemically, they guide chemokine receptor-positive circulating progenitors into the tumor bed. Subsequently, endothelial progenitors are truly integrated into the network of pre-existing vessels. This mechanism represents a novel concept where not the tumor itself, but endothelial cells as components of the tumor-induced stroma foster neovascularization in a self-amplifying loop.
机译：骨髓来源的内皮前体细胞有助于肿瘤新血管形成。但是，尚不清楚何时进行性肿瘤生长期间何时将循环的前体募集到先前存在的血管网络中，以及它们如何专门归巢到肿瘤微环境中。在这里，我们总结了多阶段致癌小鼠模型的最新发现，揭示了血管生成活性的不同阶段。只有高度异质的，发芽的脉管系统将内皮祖细胞募集到晚期的肿瘤。令人惊讶的是，在进行性肿瘤生长期间，内皮细胞具有新的特性并分泌CC趋化因子，这是一组具有相邻半胱氨酸的趋化因子，它们通过以自分泌和内分泌的方式增强新血管形成而发挥双重作用。在局部，趋化因子刺激内皮细胞的增殖。他们系统地引导趋化因子受体阳性的循环祖细胞进入肿瘤床。随后，将内皮祖细胞真正整合到已有血管网络中。该机制代表了一个新概念，其中不是肿瘤本身，而是内皮细胞作为肿瘤诱导的基质的组成部分，在自扩增环中促进了新血管形成。

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