PCL20-115: A Preclinical Study: the Role of Hypoxic Preconditioned Adipose Derived Stem Cells From Obese Breast Cancer Patients in Promoting Tumor Angiogenesis in Mouse Model

Background: Recent decades have discovered evidences that obesity is associated with a higher risk of developing breast cancer both in women and men, and even with worse disease outcome. Although the development of breast cancer was proved linked with hypoxia, there still lack of a certain conclusion in the exact mechanism how breast cancer related with obesity and hypoxia. This study aimed to identify the detailed mechanism through hypoxic preconditioned adipose-derived stem cells (ADSC) from breast cancer patients and find out their role in angiogenesis. Materials and methods: ADSC were isolated from subcutaneous adipose tissue, which were approved by 14 clinical breast cancer patients with mastectomy, ages from 30 to 60 years old, admitted in Zhongnan Hospital, Wuhan University from November 2017 to September 2018. After 2 to 3 passages, ADSC were preconditioned in hypoxic incubator (5% oxygen) for 24 hours. The supernatant culture medium from the hypoxic ones and normal oxygen ones were respectfully applied to examine their effect on human umbilical vein endothelial Cells (HUVEC). And the Elisa assays were applied in measuring the angiogenic factors involved, such as vascular endothelial growth factor (VEGF)-A and fibroblast growth factor (FGF) 2. In addition, human parathyroid adenoma tissues were transplanted into nude mice, respectfully co-transplanted with hypoxic preconditioned and normal oxygen cultured ADSC, examining the tumor growth and angiogenesis in vivo. Results: Hypoxic pretreated ADSC supernatant had various effects on cell proliferation, migration and tube formation in ADSC, HUVEC and adenoma growth. The supernatant of hypoxic conditioned ADSCs (6 different samples from breast cancer patients) induced tubule formation and promoted migration of ADSC and HUVEC compared with those from normal oxygen ones. Contemporary samples increased blood vessel density around transplanted tissues, as well as higher expression of VEGF-A and FGF2. Those hypoxic preconditioned ADSCs with positive angiogenic function were got from Breast cancer patients with obesity (BMI in 31.01±1.46 kg/m2, mean ± SD). Conclusions: The results above suggested the hypoxic condition provided an environment for ADSC in obese patients through regulating the expression of angiogenic factors. Further research will not only examine the detailed mechanism involved in HIF1a signaling and angiogenesis signaling pathways, but also explore reagents in suppressing the procedure.

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Corresponding Author: Qiuxia Cui, MD
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