title: Tumor endothelial expression of P-glycoprotein upon microvesicular transfer of TrpC5 derived from adriamycin-resistant breast cancer cells.
abstract: Treatment of carcinoma commonly fails due to chemoresistance. Studies have shown that endothelial cells acquire resistance via the tumor microenvironment. Microvesicle (MV) shedding from the cell membrane to the microenvironment plays an important role in communication between cells. The aim of the present study was to determine whether MCF-7 adriamycin-resistant cells (MCF-7/ADM) shed MVs that alter the characteristics of human microvessel endothelial cells (HMECs). MVs from tumor cells transferred a Ca(2+)-permeable channel TrpC5 to HMECs, inducing the expression of P-glycoprotein (P-gp) by activation of the transcription factor NFATc3 (nuclear factor of activated T cells isoform c3). Expression of the mdr1 gene was blocked by the TrpC5-blocking antibody T5E3, and the production of P-gp in HMECs was reduced by blockade of TrpC5. Thus, we postulate that endothelial cells acquire the resistant protein upon exposure to TrpC5-containg MVs in the microenvironment, and express P-gp in the TrpC5-NFATc3 signal pathway.
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu 214122, China.
authors.forename: YePing
authors.initials: Y
authors.lastname: Dong
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu 214122, China.
authors.forename: QiongXi
authors.initials: Q
authors.lastname: Pan
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: Zhen
authors.initials: Z
authors.lastname: Chen
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu 214122, China.
authors.forename: FangFang
authors.initials: F
authors.lastname: Zhang
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu 214122, China.
authors.forename: YanJun
authors.initials: Y
authors.lastname: Liu
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: Jiao
authors.initials: J
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu 214122, China.
authors.forename: XiYuan
authors.initials: X
authors.lastname: Li
authors.affiliation: School of Pharmaceutical Sciences, Jiangnan University, 1800 Lihu Rd, Wuxi, Jiangsu 214122, China.
authors.forename: YaoDan
authors.initials: Y
authors.lastname: Zhu
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 / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism*; D002450:Cell Communication; D055252:Cell-Derived Microparticles / Q000378:metabolism; D002478:Cells, Cultured; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D064593:Heterografts; D006801:Humans; D061986:MCF-7 Cells; D051379:Mice; D008819:Mice, Nude; D050778:NFATC Transcription Factors / Q000378:metabolism*; D015398:Signal Transduction; D050052:TRPC Cation Channels / Q000378:metabolism*; D059016:Tumor Microenvironment
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D050778:NFATC Transcription Factors; C494008:NFATC3 protein, human; D050052:TRPC Cation Channels; C491780:TRPC5 protein, human; D004317:Doxorubicin
keywords: Drug-resistant; Endothelial cells; Microvesicles; P-gp expression