title: Breast cancer resistance protein (BCRP)-containing circulating microvesicles contribute to chemoresistance in breast cancer.
abstract: At present, one of the major problems of cancer therapy is drug resistance. Breast cancer resistance protein (BCRP), a marker of the multidrug-resistant phenotype, affects drug absorption, distribution, metabolism, and excretion in normal tissues. Meanwhile, extracellular vesicles (EVs) have attracted increasing attention as a medium of cell-to-cell communication. However, the association between BCRP and circulating EVs remains unclear. The present study demonstrated that patients who did not respond or had progressive/stable disease following chemotherapy had markedly higher BCRP levels compared to those that did not receive chemotherapy. Moreover, BCRP was upregulated at the mRNA and protein levels in tumor-derived circulating EVs from patients with a poor response to chemotherapy. Interestingly, the results also demonstrated that BCRP was co-expressed with MUC1, which is frequently expressed in breast cancer and is exported via EVs, and both BCRP and MUC1 were up-regulated after chemotherapy. In conclusion, the present study indicates that tumor-derived circulating EVs that carry BCRP may serve as a predictive biomarker of the response to chemotherapy for breast cancer. In addition, the results provide a window for individualized treatment to overcome resistance to chemotherapeutic drugs.
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, Wuxi, Jiangsu 214122, P.R. China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Medical Oncology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 204062, P.R. China.
authors.forename: Linjun
authors.initials: L
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, Wuxi, Jiangsu 214122, P.R. China.
authors.forename: Yifei
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, Wuxi, Jiangsu 214122, P.R. China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Pathology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 204062, P.R. China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Qi
authors.affiliation: Department of Pathology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 204062, P.R. China.
authors.forename: Linfang
authors.initials: L
authors.lastname: Jin
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, Wuxi, Jiangsu 214122, P.R. China.
authors.forename: Jian
authors.initials: J
authors.lastname: Jin
authors.affiliation: Department of Medical Oncology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 204062, P.R. China; Department of Pathology, Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu 204062, P.R. China.
authors.forename: Dong
authors.initials: D
authors.lastname: Hua
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, Wuxi, Jiangsu 214122, P.R. China.
authors.forename: Xin
authors.initials: X
authors.lastname: Ma
keywords: breast cancer resistance protein; chemotherapeutic resistance; extracellular vesicles; mucin 1; predictive biomarker