Tumor and Stem Cell Biology TheWhite Adipose TissueUsed in Lipotransfer Procedures Is a Rich Reservoir of CD34þ Progenitors Able to Promote Cancer Progression

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-CD34þ EPCs with endothelial differentiation potential, containing a mean of 263 times more CD45-CD34þ cells/mL than bone marrow. Compared with marrow-derived CD34þ cells mobilized in blood by granulocyte colony–stimulating factor, purified WAT-CD34þ cells expressed similar levels of stemness-related genes, significantly increased levels of angiogenesis-related genes, and increased levels of FAP-a, a crucial suppressor of antitumor immunity. In vitro, WAT-CD34þ cells generated mature endothelial cells and capillary tubes as efficiently as mature mesenchymal cells. The coinjection of human WAT-CD34þ cells from lipotransfer procedures contributed to tumor vascularization and significantly increased tumor growth andmetastases in several orthotopicmodels of human breast cancer in immunodeficient mice. Endothelial cells derived from human WAT-CD34þ cells lined the lumen of cancer vessels. These data indicate that CD34þ 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. 2011 AACR.