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首页> 外文期刊>Nature >In vivo imaging of specialized bone marrow endothelial microdomains for tumour engraftment
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In vivo imaging of specialized bone marrow endothelial microdomains for tumour engraftment

机译：肿瘤植入专用骨髓内皮微区的体内成像

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摘要

The organization of cellular niches is known to have a key role in regulating normal stem cell differentiation and regeneration, but relatively little is known about the architecture of microenvironments that support malignant metastasis(1,2). Using dynamic in vivo confocal imaging, here we show that murine bone marrow contains unique anatomic regions defined by specialized endothelium. This vasculature expresses the adhesion molecule E-selectin and the chemoattractant stromal-cell-derived factor 1 (SDF-1) in discrete, discontinuous areas that influence the homing of a variety of tumour cell lines. Disruption of the interactions between SDF-1 and its receptor CXCR4 inhibits the homing of Nalm-6 cells (an acute lymphoblastic leukaemia cell line) to these vessels. Further studies revealed that circulating leukaemic cells can engraft around these vessels, suggesting that this molecularly distinct vasculature demarcates a microenvironment for early metastatic tumour spread in bone marrow. Finally, purified haematopoietic stem/progenitor cells and lymphocytes also localize to the same microdomains, indicating that this vasculature might also function in benign states to demarcate specific portals for the entry of cells into the marrow space. Specialized vascular structures therefore appear to delineate a microenvironment with unique physiology that can be exploited by circulating malignant cells.
机译：已知细胞壁ches的组织在调节正常干细胞的分化和再生中起着关键作用，但对支持恶性转移的微环境的结构知之甚少（1,2）。使用动态体内共聚焦成像，在这里我们显示鼠骨髓中包含由专门的内皮细胞定义的独特解剖区域。该脉管系统在影响各种肿瘤细胞系归巢的离散，不连续区域表达粘附分子E-选择蛋白和趋化性基质细胞衍生因子1（SDF-1）。 SDF-1及其受体CXCR4之间相互作用的破坏抑制了Nalm-6细胞（一种急性淋巴细胞白血病细胞系）向这些血管的归巢。进一步的研究表明，循环中的白血病细胞可以移植到这些血管周围，这表明这种分子上独特的脉管系统为早期转移性肿瘤在骨髓中的扩散界定了微环境。最后，纯化的造血干/祖细胞和淋巴细胞也定位于相同的微区，表明该脉管系统也可能以良性状态发挥作用，以划定特定的入口，使细胞进入骨髓空间。因此，专门的血管结构似乎描绘出具有独特生理学的微环境，可通过循环恶性细胞加以利用。

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