Microvesicles mediate transfer of P-glycoprotein to paclitaxel-sensitive A2780 human ovarian cancer cells, conferring paclitaxel-resistance

Zhang, Fang-Fang; Zhu, Yifei; Zhao, Qiannan; Yang, Dantong; Dong, Yeping; Jiang, Li; Xing, Wei-xing; Li, Xiyuan; Xing, Hui; Shi, Mei; Chen, Yun; Bruce, Iain C.; Jin, Jian; Ma, Xin

doi:10.1016/j.ejphar.2014.05.026

Cited by 89 publications

(58 citation statements)

References 27 publications

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“…We also elucidated that the release of exosomes by MCF-7/ADR cells enables drug resistance not only by transferring exosomes carrying MDR-1 mRNA and its product P-gp, also by removing anticancer drugs that have entered the cells. As we’ve seen in other studies, the different reversal fold changes may be associated with different incubation time and different amount of exosomes [29]. Exosomes may also negatively impact chemotherapy treatment by shuttling out chemotherapeutic agents from target cancer cells.…”

Section: Discussionmentioning

confidence: 83%

Exosomes play an important role in the process of psoralen reverse multidrug resistance of breast cancer

Wang

Hua

et al. 2016

J Exp Clin Cancer Res

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BackgroundRelease of exosomes have been shown to play critical roles in drug resistance by delivering cargo. Targeting the transfer of exosomes from resistant cells to sensitive cells may be an approach to overcome some cases of drug resistance.MethodIn this study, we investigated the potential role of exosomes in the process of psoralen reverse multidrug resistance of MCF-7/ADR cells. Exosomes were isolated by differential centrifugation of culture media from MCF-7/ADR cells (ADR/exo) and MCF-7 parental cells (S/exo). Exosomes were characterized by morphology, exosomal markers and size distribution. The ability of ADR/exo to transfer multidrug resistance was assessed by MTT and real-time quantitative PCR. The different formation and secretion of exosomes were detected by immunofluorescence and transmission electron microscopy. Then we performed comparative transcriptomic analysis using RNA-Seq technology and real-time quantitative PCR to better understand the gene expression regulation in exosmes formation and release after psoralen treatment.ResultsOur data showed that exosomes derived from MCF-7/ADR cells were able to promote active sequestration of drugs and could induce a drug resistance phenotype by transferring drug-resistance-related gene MDR-1 and P-glycoprotein protein. Psoralen could reduce the formation and secretion of exosomes to overcome drug resistance. There were 21 differentially expressed genes. Gene ontology (GO) pathway analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the most significantly expressed genes were linked to PPAR and P53 signaling pathways which were related to exosomes formation, secretion and cargo sorting.ConclusionsPsoralen can affect the exosomes and induce the reduction of resistance transmission via exosomes might through PPAR and P53 signaling pathways, which might provide a novel strategy for breast cancer resistance to chemotherapy in the future.

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Section: Discussionmentioning

confidence: 83%

Exosomes play an important role in the process of psoralen reverse multidrug resistance of breast cancer

Wang

Hua

et al. 2016

J Exp Clin Cancer Res

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“…Modes of intercellular transport that have been well-studied include chemical signaling via cytokines or other diffusible signals, packaging of signals in membrane-enclosed vesicles such as exosomes or microvesicles, and connexin-based gap junctions connecting adjacent cells [4, 5]. Tunneling nanotubes (TNTs) have recently been characterized as cellular conduits of intercellular communication increasingly studied for their role in mediating long-range transport of cellular cargo via direct cell-to-cell contact [6–14].…”

Section: Introductionmentioning

confidence: 99%

Tunneling nanotube formation is stimulated by hypoxia in ovarian cancer cells

et al. 2016

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In this study, we demonstrated that hypoxic conditions stimulated an increase in tunneling nanotube (TNT) formation in chemoresistant ovarian cancer cells (SKOV3, C200). We found that suppressing the mTOR pathway using either everolimus or metformin led to suppression of TNT formation in vitro, verifying TNTs as a potential target for cancer-directed therapy. Additionally, TNT formation was detected in co-cultures including between platinum-resistant SKOV3 cells, between SKOV3 cells and platinum-chemosensitive A2780 cells, and between SKOV3 cells cultured with benign ovarian epithelial (IOSE) cells; these findings indicate that TNTs are novel conduits for malignant cell interactions and tumor cell interactions with other cells in the microenvironment. When chemoresistant C200 and parent chemosensitive A2780 cells were co-cultured, chemoresistant cells displayed a higher likelihood of TNT formation to each other than to chemosensitive malignant or benign epithelial cells. Hypoxia-induced TNT formation represents a potential mechanism for intercellular communication in ovarian cancer and other forms of invasive refractory cancers.

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“…In this study, the transfer of functional P-gp to the drugsensitive recipient cells was also observed [31].…”

Section: Transfer Of Drug Resistance Traits By Evs: Drug-efflux Pumpsmentioning

confidence: 78%

Intercellular Transfer of Cancer Drug Resistance Traits by Extracellular Vesicles

Sousa

Lima

Vasconcelos

2015

Trends in Molecular Medicine

143

138

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Microvesicles mediate transfer of P-glycoprotein to paclitaxel-sensitive A2780 human ovarian cancer cells, conferring paclitaxel-resistance

Cited by 89 publications

References 27 publications

Exosomes play an important role in the process of psoralen reverse multidrug resistance of breast cancer

Exosomes play an important role in the process of psoralen reverse multidrug resistance of breast cancer

Tunneling nanotube formation is stimulated by hypoxia in ovarian cancer cells

Intercellular Transfer of Cancer Drug Resistance Traits by Extracellular Vesicles

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