Premium
UCH‐L1‐containing exosomes mediate chemotherapeutic resistance transfer in breast cancer
Author(s) -
Ning Kuan,
Wang Teng,
Sun Xu,
Zhang Pengfei,
Chen Yun,
Jin Jian,
Hua Dong
Publication year - 2017
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.24614
Subject(s) - microvesicles , breast cancer , medicine , cancer research , exosome , flow cytometry , immunostaining , cancer , western blot , extracellular , chemotherapy , cancer cell , pathology , immunohistochemistry , immunology , biology , microrna , microbiology and biotechnology , biochemistry , gene
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.