UCH-L1-containing exosomes mediate chemotherapeutic resistance transfer in breast cancer.
J Surg Oncol
; 115(8): 932-940, 2017 Jun.
Article
em En
| MEDLINE
| ID: mdl-28334432
ABSTRACT
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.Palavras-chave
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MEDLINE
Assunto principal:
Neoplasias da Mama
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Membro 1 da Subfamília B de Cassetes de Ligação de ATP
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Resistencia a Medicamentos Antineoplásicos
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Ubiquitina Tiolesterase
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Exossomos
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article