Abstract 1019: CD34+ progenitors resident in the human white adipose tissue promote tumor angiogenesis, growth and metastases in orthotopic models of breast cancer

Abstract

Abstract Similarly to neoplasia, the human white adipose tissue (WAT) shows in vivo a robust angiogenic switch when the growth rate exceeds a given expansion threshold. Also, anti-angiogenic drugs have been found to inhibit WAT development in postnatal mice. We have recently reported that the human WAT is very rich in CD45-CD34+ progenitors that express high levels of angiogenesis-related genes and can generate in culture endothelial cells and tubes as efficiently as mesenchymal cells (Martin-Padura et al, Cancer Res, in the press). Compared to the bone marrow, WAT contains >250 times more CD45-CD34+ progenitors with endothelial differentiation potential. The co-injection of human WAT-derived CD45-CD34+ progenitors from lipotransfer procedures contributed to tumor vascularization and significantly increased tumor growth and metastases in several orthotopic models of human breast cancer in immunodeficient NSG mice. At variance with human bone marrow-derived CD34+ progenitors, which were found to incorporate only in perivascular sites of tumor vasculature, confocal z-stack studies showed that mature endothelial cells derived from human WAT-CD34+ progenitors lined the lumen of fully functional cancer vessels where red cells were found to circulate. Transwell and 3D time-lapse studies in collagen showed that human WAT cells significantly promoted an EMT switch as well as breast cancer cell directionality, migration and invasion towards a gradient of several different chemo-attractants. Autologous lipotransfer for tissue/organ reconstruction is used in patients who had surgical removal of breast and other types of cancer. We have recently reported a study of 321 consecutive patients operated for primary breast cancer who subsequently underwent a lipotransfer procedure, compared with two matched patients with similar characteristics who did not undergo lipotransfer (Petit et al, Ann Oncol, in the press). In this study, the lipotransfer group exhibited a higher risk of local events compared to the controls when the analysis was limited to intraepithelial neoplasia. A second data revision after prolonged follow-up confirmed this significant difference. The dissection of the different roles of purified populations of WAT-derived progenitors and mature cells seems urgent to clarify which WAT cell populations can be used safely for breast reconstruction in cancer patients. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1019. doi:1538-7445.AM2012-1019