Endothelial progenitor cells from infantile hemangioma and umbilical cord blood display unique cellular responses to endostatin
Endothelial progenitor cells from infantile hemangioma and umbilical cord blood display unique cellular responses to endostatin
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DOI：
10.1182/blood-2006-03-006478
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发表时间：
2006-08-01
期刊：
影响因子：
20.3
通讯作者：
Bischoff, Joyce
中科院分区：
文献类型：
--
作者：
Khan, Zia A.;Melero-Martin, Juan M.;Bischoff, Joyce
婴儿血管瘤由内皮细胞、内皮祖细胞、血管周围细胞和造血细胞组成。我们的假设是，血管瘤源性内皮祖细胞（HemEPCs）分化为成熟的内皮细胞，构成了肿瘤的主要部分。为了测试这一点，我们从增殖的血管瘤中分离出EPCs（CD 133（+）/U/ex europeus-l+）抗成熟EC（CD 133（-）/U/ex europeus 1（+）），并使用先前描述的血管瘤衍生的EC（HemEC）的特性，即响应于血管生成抑制剂内皮抑制素的增强的迁移活性，来确定HemEPCs是否具有这种异常行为。以脐带血来源的EPCs（cbEPCs）作为正常对照进行平行分析。我们的研究结果表明，HemEPCs，HemECs和cbEPCs表现出增加的粘附，迁移和增殖响应内皮抑素。这种血管生成反应内皮抑制素表达的HemEPCs在几个星期的文化，而HemECs和cbEPCs转向成熟的内皮再表达模式之间HemEPCs，HemECs，和cbEPCs，微阵列分析显示，提供了进一步的EPC表型的迹象。这是第一次证明，从血液或从增殖的血管瘤中分离的人EPCs，被血管生成抑制剂刺激。这些结果表明，EPCs的反应不同于成熟的EC时，暴露于血管生成或antlangiogenic信号。对内皮抑制素应答。微阵列分析显示，HemEPCs，HemECs和cbEPCs之间的mRNA表达模式相似，进一步表明了EPC表型。这是第一次证明，从血液或从增殖的血管瘤中分离的人EPCs，被血管生成抑制剂刺激。这些结果表明，EPCs的反应不同于成熟的EC时，暴露于血管生成或antlangiogenic信号。
Infantile hemanglomas are composed of endothelial cells (ECs), endothelial progenitor cells (EPCs), as well as perivascular and hematopoletic cells. Our hypothesis is that hemangioma-derived EPCs (HemEPCs) differentiate into the mature ECs that comprise the major compartment of the tumor. To test this, we isolated EPCs (CD133(+)/U/ex europeus-l+) anti mature ECs (CD133(-)lUiex europeus1(+)) from proliferating hemanglomas and used a previously described property of heinangioma-derived ECs (HemECs), enhanced migratory activity in response to the angiogenesis inhibitor endostatin, to determine if HemEPCs share this abnormal behavior. Umbilical cord bloodderived EPCs (cbEPCs) were analyzed in parallel as a normal control. Our results show that HemEPCs, HemECs, and cbEPCs exhibit increased adhesion, migration, and proliferation in response to endostatin. This angiogenic response to endostatin was consistently expressed by HemEPCs over several weeks in culture, whereas HemECs and cbEPCs shifted toward the mature endothelial re-expression patterns among HemEPCs, HemECs, and cbEPCs, revealed by microarray analyses, provided further indication of an EPC phenotype. This is the first demonstration that human EPCs, isolated from blood or from a proliferating hemangloma, are stimulated by an anglogenesis inhibitor. These findings suggest that EPCs respond differently from mature ECs when exposed to anglogenic or antlangiogenic signals. sponse to endostatin. Similar mRNA-expression patterns among HemEPCs, HemECs, and cbEPCs, revealed by microarray analyses, provided further indication of an EPC phenotype. This is the first demonstration that human EPCs, isolated from blood or from a proliferating hemangloma, are stimulated by an anglogenesis inhibitor. These findings suggest that EPCs respond differently from mature ECs when exposed to anglogenic or antlangiogenic signals.