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.


RESULTS
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.


CONCLUSIONS
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.
Department of Oncology, Affiliated Hospital of Jiangnan University and the Fourth People's Hospital of Wuxi, Wuxi, Jiangsu, China.|Wuxi Medical College, Jiangnan University, Wuxi, Jiangsu, China.
Kuan
http://orcid.org/0000-0001-8660-4283
K
Ning
Department of Oncology, Affiliated Hospital of Jiangnan University and the Fourth People's Hospital of Wuxi, Wuxi, Jiangsu, China.
Teng
T
Wang
Department of Oncology, Affiliated Hospital of Jiangnan University and the Fourth People's Hospital of Wuxi, Wuxi, Jiangsu, China.
Xu
X
Sun
Wuxi Medical College, Jiangnan University, Wuxi, Jiangsu, China.
Pengfei
P
Zhang
School of Pharmaceutical Sciences, Jiangnan University, Wuxi, Jiangsu, China.
Yun
Y
Chen
School of Pharmaceutical Sciences, Jiangnan University, Wuxi, Jiangsu, China.
Jian
J
Jin
Department of Oncology, Affiliated Hospital of Jiangnan University and the Fourth People's Hospital of Wuxi, Wuxi, Jiangsu, China.
Dong
D
Hua
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D018929:Cell Culture Techniques; D004317:Doxorubicin / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D055354:Exosomes / Q000502:physiology*; D005260:Female; D006801:Humans; D008875:Middle Aged; D043222:Ubiquitin Thiolesterase / Q000378:metabolism*
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D004317:Doxorubicin; D043222:Ubiquitin Thiolesterase
UCH-L1; breast cancer; chemotherapeutic resistance transfer; exosomes