The White Adipose Tissue Used in Lipotransfer Procedures Is a Rich Reservoir of CD34+ Progenitors Able to Promote Cancer Progression
The White Adipose Tissue Used in Lipotransfer Procedures Is a Rich Reservoir of CD34+ Progenitors Able to Promote Cancer Progression
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DOI：
10.1158/0008-5472.can-11-1739
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发表时间：
2012-01-01
期刊：
影响因子：
11.2
通讯作者：
Bertolini, Francesco
中科院分区：
文献类型：
--
作者：
Martin-Padura, Ines;Gregato, Giuliana;Bertolini, Francesco
以前的研究表明，骨髓来源的内皮祖细胞(EPC)在肿瘤血管生成和癌症进展中具有“催化作用”。然而，临床前和临床研究表明，骨髓来源的内皮祖细胞在肿瘤血管形成中的定量作用是非常不同的。我们发现人和小鼠白色脂肪组织(WAT)是一个非常丰富的具有内皮分化潜能的CD45-CD34(+)内皮祖细胞储存库，其平均CD45-CD34(+)细胞/毫升是骨髓的263倍。与粒细胞集落刺激因子动员的骨髓CD34(+)细胞相比，纯化的Wat-CD34(+)细胞表达类似水平的干细胞相关基因，显著增加血管生成相关基因的水平，并增加抗肿瘤免疫的关键抑制因子FAP-α的水平。在体外，Wat-CD34(+)细胞生成成熟的内皮细胞和毛细血管的效率与成熟的间充质细胞相同。在免疫缺陷小鼠的几种人乳腺癌原位模型中，共注射来自脂转移程序的人Wat-CD34(+)细胞有助于肿瘤血管的形成，并显著增加肿瘤的生长和转移。来源于人类Wat-CD34(+)细胞的内皮细胞排列在肿瘤血管的管腔内。这些数据表明CD34(+)Wat细胞可以促进癌症的进展和转移。我们的结果强调了更好地了解不同的Wat来源的细胞在乳腺癌患者的乳房重建中用于脂转移的作用的重要性。癌症资源；72(1)；325-34。(C)2011年AACR。
Previous studies have suggested a "catalytic role" in neoplastic angiogenesis and cancer progression for bone marrow-derived endothelial progenitor cells (EPC). However, preclinical and clinical studies have shown that the quantitative role of marrow-derived EPCs in cancer vascularization is extremely variable. We have found that human and murine white adipose tissue (WAT) is a very rich reservoir of CD45-CD34(+) EPCs with endothelial differentiation potential, containing a mean of 263 times more CD45-CD34(+) cells/mL than bone marrow. Compared with marrow-derived CD34(+) cells mobilized in blood by granulocyte colony-stimulating factor, purified WAT-CD34(+) cells expressed similar levels of stemness-related genes, significantly increased levels of angiogenesis-related genes, and increased levels of FAP-alpha, a crucial suppressor of antitumor immunity. In vitro, WAT-CD34(+) cells generated mature endothelial cells and capillary tubes as efficiently as mature mesenchymal cells. The coinjection of human WAT-CD34(+) cells from lipotransfer procedures contributed to tumor vascularization and significantly increased tumor growth and metastases in several orthotopic models of human breast cancer in immunodeficient mice. Endothelial cells derived from human WAT-CD34(+) cells lined the lumen of cancer vessels. These data indicate that CD34(+) WAT cells can promote cancer progression and metastases. Our results highlight the importance of gaining a better understanding of the role of different WAT-derived cells used in lipotransfer for breast reconstruction in patients with breast cancer. Cancer Res; 72(1); 325-34. (C) 2011 AACR.