Background: Mesenchymal stem cells in tumor microenvironment can influence therapeutic responses in various
types of cancers. For triple negative breast cancer, chemotherapy remains the mainstay of standard treatment. Our
aim was to investigate the correlation between human adipose-derived stem cells (hAdSCs) and chemoresistance
in triple negative breast cancer.
Method: Conditioned medium was collected from hAdSCs, which was isolated from breast cancer patients
who had had breast mastectomy. The expression of selected CD markers was evaluated by flow cytometry to
characterize hAdSCs. By array analyses of the secreted cytokines and chemokines of hAdSCs, we identified
CXCL1 that mediated doxorubicin resistance and the expression of ATP-binding cassette transporters ABCG2 in
TNBC. By microRNA microarray, the association between hAdSC-mediated doxorubicin resistance in TNBC was
also revealed.
Results: Conditioned medium collected from hAdSCs elicited doxorubicin resistance and enhanced the
expression of ABCG2, which is a transporter responsible for the efflux of doxorubicin. CXCL1 secreted by
hAdSCs downregulated miR-106a expression in triple negative breast cancer, and resulted in ABCG2
upregulation and doxorubicin resistance.
Conclusions: Our findings suggest that CXCL1 secreted by hAdSCs elicits doxorubicin resistance through
miR-106a-mediated ABCG2 upregulation in triple negative breast cancer. These findings provide a better
understanding of the importance of adipose-derived stem cells in breast cancer microenvironment regarding
to the development of chemoresistance and reveal the potential of discovering novel therapeutic strategies to
overcome drug resistance in TNBC.
Keywords: Adipose-derived stem cells, ABCG2, Drug resistance, Triple negative breast cancer
