UCH-L1-containing exosomes mediate chemotherapeutic resistance transfer in breast cancer

Background: Chemotherapy resistance has become a serious challenge in the treatment of breast Cancer. Previous studies showed cells can transfer proteins, including those responsible for drug resistance to adjacent cells via exosomes.

Methods: The switches of drug resistance via exosomes transfer were assessed by CellTiter-Blue Viability assay, flow cytometry, and immunostaining analysis. Relative protein levels of Ubiquitin carboxyl terminal hydrolase-L1 (UCH-L1), P-glycoprotein (P-gp), extracellular-signal regulated protein kinase1/2 (ERK1/2), and phospho-extracellular-signal regulated protein kinase1/2 (p-ERK1/2) were measured by Western blot. Immunohistochemistry was performed on 93 breast Cancer samples to assess the associations of UCH-L1 levels with immunofluorescence value of UCH-L1 in circulating exosomes.

Result: The Adriamycin-resistant human breast Cancer cells (MCF7/ADM) secreted exosomes carrying UCH-L1 and P-gp proteins into the extracellular microenvironment then integrated into Adriamycin-sensitive human breast Cancer cells (MCF7/WT) in a time-dependent manner, transferring the chemoresistance phenotype. Notably, in blood samples from patients with breast Cancer, the level of exosomes carrying UCH-L1 before chemotherapy was significantly negatively correlated with prognosis.

Conclusion: Our study demonstrated that UCH-L1-containing exosomes can transfer chemoresistance to recipient cells and these exosomes may be useful as non-invasive diagnostic biomarkers for detection of chemoresitance in breast Cancer patients, achieving more effective and individualized chemotherapy.