title: Microvesicles mediate transfer of P-glycoprotein to paclitaxel-sensitive A2780 human ovarian cancer cells, conferring paclitaxel-resistance.
abstract: The overexpression of P-glycoprotein (P-gp) causes resistance to chemotherapy in human ovarian cancer. However, the underlying mechanism remains unclear. In the present study, we showed that, at membrane-bound protein level, P-gp was 'shared' between human ovarian cancer cells by the intercellular transfer of microvesicles (MVs). Paclitaxel-resistant human ovarian cancer cells (A2780/PTX) readily formed and released P-gp-containing MVs into the extracellular space compared with the wild-type parental line (A2780/WT). Shedding MVs bound to the chemosensitive A2780/WT cells in a time- and dose-dependent manner, transferring P-gp via the microenvironment. MV-mediated transfer of P-gp led to redistribution of the chemotherapeutic drug adriamycin in recipient cells (A2780/WT), which displayed 5- and 5-fold higher resistance to adriamycin and paclitaxel, respectively. Thus, these findings demonstrate a new mechanism of drug-resistance acquisition via MVs.
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu 214122, China.
authors.forename: Fang-fang
authors.initials: FF
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu 214122, China.
authors.forename: Yi-fei
authors.initials: YF
authors.lastname: Zhu
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu 214122, China.
authors.forename: Qian-nan
authors.initials: QN
authors.lastname: Zhao
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu 214122, China.
authors.forename: Dan-tong
authors.initials: DT
authors.lastname: Yang
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu 214122, China.
authors.forename: Ye-ping
authors.initials: YP
authors.lastname: Dong
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu 214122, China.
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu 214122, China.
authors.forename: Wei-xing
authors.initials: WX
authors.lastname: Xing
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu 214122, China.
authors.forename: Xi-yuan
authors.initials: XY
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu 214122, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xing
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu 214122, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Shi
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu 214122, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Chen
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu 214122, China.
authors.forename: Iain C
authors.initials: IC
authors.lastname: Bruce
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu 214122, China. Electronic address: jinjian31@126.com.
authors.forename: Jian
authors.initials: J
authors.lastname: Jin
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu 214122, China. Electronic address: maxin@jiangnan.edu.cn.
authors.forename: Xin
authors.initials: X
authors.lastname: Ma
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D018432:Drug Resistance, Multiple / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects* / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000473:pathology*; D017239:Paclitaxel / Q000494:pharmacology*; D021381:Protein Transport / Q000187:drug effects
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D017239:Paclitaxel
keywords: Adriamycin (PubChem CID: 31703); Human ovarian cancer cells; Intercellular transfer; Microvesicles; P-glycoprotein; Paclitaxel (PubChem CID:36314)