Breast cancer stem cell reprogramming using exosomes derived from human adipose stem cells during adipogenic differentiation

Abstract

Breast cancer is the most commonly occurring cancer in women and women died from breast cancer is approximately 15 % of all cancer deaths among women. Among these, breast cancer stem cells were associated with poorer prognosis, metastasis, tumor progression and drug resistance. We hypothesized exosomes derived from human adipose stem cells during adipogenic differentiation can be used to cancer therapy through reprogramming breast cancer stem cell to non-tumorigenic cells. Adipogenic differentiation exosomes (AD-Exo) were contained specific cargos that induce adipogenic differentiation, such as adiponectin and adipsin. AD-Exo were isolated during adipogenic differentiation of human adipose derived stem cell (HASC) using tangential flow filtration(TFF). AD-Exo were characterization by Nanoparticle tracking analysis, transmission electron microscopy, dynamic light scattering, zeta potential measurement and flow cytometry. After AD-Exo treated for MDA-MB-231 that has enriched CSCs, the induction into adipogenic differentiation was measured by Oil red O staining and flow cytometry, also reduced metastasis-related factors and drug resistance-related factors were analyzed by qPCR. In addition, RT2 profiler PCR array analysis revealed that AD-Exo reduced invasion, metastasis, angiogenesis and tumor progression. We suggest that AD-Exo can be used for cancer stem cell reprogramming and that the resulting decrease in drug resistance could produce better outcome in combination with chemotherapy.