Complementary Populations of Human Adipose CD34+ Progenitor Cells Promote Growth, Angiogenesis, and Metastasis of Breast Cancer
Complementary Populations of Human Adipose CD34+ Progenitor Cells Promote Growth, Angiogenesis, and Metastasis of Breast Cancer
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DOI：
10.1158/0008-5472.can-13-0821
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发表时间：
2013-10-01
期刊：
影响因子：
11.2
通讯作者：
Bertolini, Francesco
中科院分区：
文献类型：
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作者：
Orecchioni, Stefania;Gregato, Giuliana;Bertolini, Francesco
肥胖与包括绝经后乳腺癌在内的几种肿瘤疾病的发生率、发病率和死亡率的增加有关。我们发现，人类脂肪组织包含两组在乳腺癌中发挥协同作用的祖细胞。CD45(-)、CD34(+)、CD31(+)、CD13(-)、CCRL2(+)内皮细胞可生成成熟的内皮细胞和毛细血管。在缺乏CD45(-)CD34(+)CD31(-)CD13(+)CD140b(+)间充质祖细胞/脂肪基质细胞(ASC)的情况下，它们在乳腺癌中的促癌作用是有限的，ASC产生周细胞，在促进局部肿瘤生长方面比内皮细胞更有效。血管内皮细胞和血管干细胞均可诱导乳腺癌细胞上皮向间充质转化(EMT)基因的表达。内皮细胞(但不是ASCs)迁移到淋巴结和对侧新生乳腺癌病变，在那里它们产生新的血管。在体外和体内，内皮细胞在促进肿瘤迁移和诱导转移方面比ASCs更有效。粒细胞集落刺激因子(G-CSF)有效地动员内皮细胞(但不能动员ASCs)，化疗和/或CXCR4抑制剂的加入不能增加内皮细胞或ASC的血液动员。我们的发现表明，脂肪组织前体细胞在推动乳腺癌的进展和转移扩散方面起到了协同作用。(C)2013年AACR。
Obesity is associated with an increased frequency, morbidity, and mortality of several types of neoplastic diseases, including postmenopausal breast cancer. We found that human adipose tissue contains two populations of progenitors with cooperative roles in breast cancer. CD45(-)CD34(+)CD31(+)CD13(-)CCRL2(+) endothelial cells can generate mature endothelial cells and capillaries. Their cancer-promoting effect in the breast was limited in the absence of CD45(-)CD34(+)CD31(-)CD13(+)CD140b(+) mesenchymal progenitors/adipose stromal cells (ASC), which generated pericytes and were more efficient than endothelial cells in promoting local tumor growth. Both endothelial cells and ASCs induced epithelial-to-mesenchymal transition (EMT) gene expression in luminal breast cancer cells. Endothelial cells ( but not ASCs) migrated to lymph nodes and to contralateral nascent breast cancer lesions where they generated new vessels. In vitro and in vivo, endothelial cells were more efficient than ASCs in promoting tumor migration and in inducing metastases. Granulocyte colony-stimulating factor (G-CSF) effectively mobilized endothelial cells (but not ASCs), and the addition of chemotherapy and/or of CXCR4 inhibitors did not increase endothelial cell or ASC blood mobilization. Our findings suggest that adipose tissue progenitor cells cooperate in driving progression and metastatic spread of breast cancer. (c) 2013 AACR.