Identification of proangiogenic TIE2-expressing monocytes (TEMs) in human peripheral blood and cancer
Identification of proangiogenic TIE2-expressing monocytes (TEMs) in human peripheral blood and cancer
复制标题
DOI：
10.1182/blood-2006-10-053504
复制
发表时间：
2007-06-15
期刊：
影响因子：
20.3
通讯作者：
Naldini, Luigi
中科院分区：
文献类型：
--
作者：
Venneri, Mary Anna;De Palma, Michele;Naldini, Luigi
肿瘤浸润性髓样细胞，包括肿瘤相关巨噬细胞（TAM），与肿瘤进展有关。我们最近描述了小鼠单核细胞的谱系，其特征在于表达Tie 2血管紧张素受体，并且是几种肿瘤模型的血管形成和生长所需的。在这里，我们报告说，TIE 2在人类血液中的表达，确定了一个子集的单核细胞不同于经典的炎症单核细胞，并包括在较低丰度的“居民”人口。这些表达TIE 2的单核细胞（TEM）占健康供体血液单核细胞的2%至7%，与罕见的循环内皮细胞和祖细胞不同。在人类癌症患者中，TEM在血液中观察到，有趣的是，在肿瘤中，它们代表了与TAM不同的主要单核细胞群体。相反，TEM在非肿瘤组织中几乎检测不到。在体外，TEM向血管生成素-2迁移，血管生成素-2是由活化的血管内皮细胞和血管生成血管释放的TIE 2配体，表明TEM向肿瘤归巢的机制。纯化的人TEM，而不是TEM-clepleted单核细胞，显着促进异种移植的人肿瘤血管生成，表明TEM在人类癌症进展中的潜在关键作用。人TEM可以提供一种新的，生物学相关的血管生成标记物，并代表了以前未被认识到的癌症治疗靶点。
Tumor-infiltrating myeloid cells, including tumor-associated macrophages (TAMs), have been implicated in tumor progression. We recently described a lineage of mouse monocytes characterized by expression of the Tie2 anglopoletin receptor and required for the vascularization and growth of several tumor models. Here, we report that TIE2 expression in human blood identifies a subset of monocytes distinct from classical inflammatory monocytes and comprised within the less abundant "resident" population. These TIE2-expressing monocytes (TEMs) accounted for 2% to 7% of blood mononuclear cells in healthy donors and were distinct from rare circulating enclothelial cells and progenitors. In human cancer patients, TEMs were observed in the blood and, intriguingly, within the tumors, where they represented the main monocyte population distinct from TAMs. Conversely, TEMs were hardly detected in nonneoplastic tissues. In vitro, TEMs migrated toward angiopoietin-2, a TIE2 Iigand released by activated enclothelial cells and anglogenic vessels, suggesting a homing mechanism for TEMs to tumors. Purified human TEMs, but not TEM-clepleted monocytes, markedly promoted angiogenesis in xenotransplanted human tumors, suggesting a potentially critical role of TEMs in human cancer progression. Human TEMs may provide a novel, biologically relevant marker of angiogenesis and represent a previously unrecognized target of cancer therapy.