{"data":{"id":"10.6084/m9.figshare.c.2078309","type":"dois","attributes":{"doi":"10.6084/m9.figshare.c.2078309","prefix":"10.6084","suffix":"m9.figshare.c.2078309","identifiers":[],"alternateIdentifiers":[],"creators":[{"name":"Ji, Runbi","givenName":"Runbi","familyName":"Ji","affiliation":[],"nameIdentifiers":[]},{"name":"Zhang, Bin","givenName":"Bin","familyName":"Zhang","affiliation":[],"nameIdentifiers":[]},{"name":"Zhang, Xu","givenName":"Xu","familyName":"Zhang","affiliation":[],"nameIdentifiers":[]},{"name":"Xue, Jianguo","givenName":"Jianguo","familyName":"Xue","affiliation":[],"nameIdentifiers":[]},{"name":"Yuan, Xiao","givenName":"Xiao","familyName":"Yuan","affiliation":[],"nameIdentifiers":[]},{"name":"Yan, Yongmin","givenName":"Yongmin","familyName":"Yan","affiliation":[],"nameIdentifiers":[]},{"name":"Wang, Mei","givenName":"Mei","familyName":"Wang","affiliation":[],"nameIdentifiers":[]},{"name":"Zhu, Wei","givenName":"Wei","familyName":"Zhu","affiliation":[],"nameIdentifiers":[]},{"name":"Qian, Hui","givenName":"Hui","familyName":"Qian","affiliation":[],"nameIdentifiers":[]},{"name":"Xu, Wenrong","givenName":"Wenrong","familyName":"Xu","affiliation":[],"nameIdentifiers":[]}],"titles":[{"title":"Exosomes derived from human mesenchymal stem cells confer drug resistance in gastric cancer"}],"publisher":"Taylor \u0026 Francis","container":{},"publicationYear":2015,"subjects":[{"subject":"Infectious Diseases"},{"subject":"FOS: Health sciences","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Hematology"},{"subject":"Cancer"},{"subject":"Developmental Biology"},{"subject":"Biological Sciences"},{"subject":"Chemistry"},{"subject":"Biotechnology"},{"subject":"Pharmacology"},{"subject":"Molecular Biology"},{"subject":"Genetics"},{"subject":"FOS: Biological sciences","schemeUri":"http://www.oecd.org/science/inno/38235147.pdf","subjectScheme":"Fields of Science and Technology (FOS)"},{"subject":"Cell Biology"},{"subject":"Medicine"},{"subject":"Biochemistry"},{"subject":"Biophysics"}],"contributors":[],"dates":[{"date":"2015-12-05","dateType":"Created"},{"date":"2019-08-19","dateType":"Updated"},{"date":"2015","dateType":"Issued"}],"language":null,"types":{"ris":"GEN","bibtex":"misc","citeproc":"article","schemaOrg":"Collection","resourceType":"Collection","resourceTypeGeneral":"Collection"},"relatedIdentifiers":[],"relatedItems":[],"sizes":[],"formats":[],"version":null,"rightsList":[{"rights":"Creative Commons Attribution 4.0 International","rightsUri":"https://creativecommons.org/licenses/by/4.0/legalcode","schemeUri":"https://spdx.org/licenses/","rightsIdentifier":"cc-by-4.0","rightsIdentifierScheme":"SPDX"}],"descriptions":[{"description":"Mesenchymal stem cells (MSCs) play an important role in chemoresistance. Exosomes have been reported to modify cellular phenotype and function by mediating cell-cell communication. In this study, we aimed to investigate whether exosomes derived from MSCs (MSC-exosomes) are involved in mediating the resistance to chemotherapy in gastric cancer and to explore the underlying molecular mechanism. We found that MSC-exosomes significantly induced the resistance of gastric cancer cells to 5-fluorouracil both in vivo and ex vivo. MSC-exosomes antagonized 5-fluorouracil-induced apoptosis and enhanced the expression of multi-drug resistance associated proteins, including MDR, MRP and LRP. Mechanistically, MSC-exosomes triggered the activation of calcium/calmodulin-dependent protein kinases (CaM-Ks) and Raf/MEK/ERK kinase cascade in gastric cancer cells. Blocking the CaM-Ks/Raf/MEK/ERK pathway inhibited the promoting role of MSC-exosomes in chemoresistance. Collectively, MSC-exosomes could induce drug resistance in gastric cancer cells by activating CaM-Ks/Raf/MEK/ERK pathway. Our findings suggest that MSC-exosomes have profound effects on modifying gastric cancer cells in the development of drug resistance. Targeting the interaction between MSC-exosomes and cancer cells may help improve the efficacy of chemotherapy in gastric cancer.","descriptionType":"Abstract"}],"geoLocations":[],"fundingReferences":[],"xml":"PD94bWwgdmVyc2lvbj0iMS4wIiBlbmNvZGluZz0iVVRGLTgiPz4KPHJlc291cmNlIHhtbG5zPSJodHRwOi8vZGF0YWNpdGUub3JnL3NjaGVtYS9rZXJuZWwtNCIgeG1sbnM6eHNpPSJodHRwOi8vd3d3LnczLm9yZy8yMDAxL1hNTFNjaGVtYS1pbnN0YW5jZSIgeHNpOnNjaGVtYUxvY2F0aW9uPSJodHRwOi8vZGF0YWNpdGUub3JnL3NjaGVtYS9rZXJuZWwtNCBodHRwOi8vc2NoZW1hLmRhdGFjaXRlLm9yZy9tZXRhL2tlcm5lbC00LjQvbWV0YWRhdGEueHNkIj4KICA8aWRlbnRpZmllciBpZGVudGlmaWVyVHlwZT0iRE9JIj4xMC42MDg0L005LkZJR1NIQVJFLkMuMjA3ODMwOTwvaWRlbnRpZmllcj4KICA8Y3JlYXRvcnM+CiAgICA8Y3JlYXRvcj4KICAgICAgPGNyZWF0b3JOYW1lPlJ1bmJpIEppPC9jcmVhdG9yTmFtZT4KICAgICAgPGdpdmVuTmFtZT5SdW5iaTwvZ2l2ZW5OYW1lPgogICAgICA8ZmFtaWx5TmFtZT5KaTwvZmFtaWx5TmFtZT4KICAgIDwvY3JlYXRvcj4KICAgIDxjcmVhdG9yPgogICAgICA8Y3JlYXRvck5hbWU+QmluIFpoYW5nPC9jcmVhdG9yTmFtZT4KICAgICAgPGdpdmVuTmFtZT5CaW48L2dpdmVuTmFtZT4KICAgICAgPGZhbWlseU5hbWU+Wmhhbmc8L2ZhbWlseU5hbWU+CiAgICA8L2NyZWF0b3I+CiAgICA8Y3JlYXRvcj4KICAgICAgPGNyZWF0b3JOYW1lPlh1IFpoYW5nPC9jcmVhdG9yTmFtZT4KICAgICAgPGdpdmVuTmFtZT5YdTwvZ2l2ZW5OYW1lPgogICAgICA8ZmFtaWx5TmFtZT5aaGFuZzwvZmFtaWx5TmFtZT4KICAgIDwvY3JlYXRvcj4KICAgIDxjcmVhdG9yPgogICAgICA8Y3JlYXRvck5hbWU+Smlhbmd1byBYdWU8L2NyZWF0b3JOYW1lPgogICAgICA8Z2l2ZW5OYW1lPkppYW5ndW88L2dpdmVuTmFtZT4KICAgICAgPGZhbWlseU5hbWU+WHVlPC9mYW1pbHlOYW1lPgogICAgPC9jcmVhdG9yPgogICAgPGNyZWF0b3I+CiAgICAgIDxjcmVhdG9yTmFtZT5YaWFvIFl1YW48L2NyZWF0b3JOYW1lPgogICAgICA8Z2l2ZW5OYW1lPlhpYW88L2dpdmVuTmFtZT4KICAgICAgPGZhbWlseU5hbWU+WXVhbjwvZmFtaWx5TmFtZT4KICAgIDwvY3JlYXRvcj4KICAgIDxjcmVhdG9yPgogICAgICA8Y3JlYXRvck5hbWU+WW9uZ21pbiBZYW48L2NyZWF0b3JOYW1lPgogICAgICA8Z2l2ZW5OYW1lPllvbmdtaW48L2dpdmVuTmFtZT4KICAgICAgPGZhbWlseU5hbWU+WWFuPC9mYW1pbHlOYW1lPgogICAgPC9jcmVhdG9yPgogICAgPGNyZWF0b3I+CiAgICAgIDxjcmVhdG9yTmFtZT5NZWkgV2FuZzwvY3JlYXRvck5hbWU+CiAgICAgIDxnaXZlbk5hbWU+TWVpPC9naXZlbk5hbWU+CiAgICAgIDxmYW1pbHlOYW1lPldhbmc8L2ZhbWlseU5hbWU+CiAgICA8L2NyZWF0b3I+CiAgICA8Y3JlYXRvcj4KICAgICAgPGNyZWF0b3JOYW1lPldlaSBaaHU8L2NyZWF0b3JOYW1lPgogICAgICA8Z2l2ZW5OYW1lPldlaTwvZ2l2ZW5OYW1lPgogICAgICA8ZmFtaWx5TmFtZT5aaHU8L2ZhbWlseU5hbWU+CiAgICA8L2NyZWF0b3I+CiAgICA8Y3JlYXRvcj4KICAgICAgPGNyZWF0b3JOYW1lPkh1aSBRaWFuPC9jcmVhdG9yTmFtZT4KICAgICAgPGdpdmVuTmFtZT5IdWk8L2dpdmVuTmFtZT4KICAgICAgPGZhbWlseU5hbWU+UWlhbjwvZmFtaWx5TmFtZT4KICAgIDwvY3JlYXRvcj4KICAgIDxjcmVhdG9yPgogICAgICA8Y3JlYXRvck5hbWU+V2Vucm9uZyBYdTwvY3JlYXRvck5hbWU+CiAgICAgIDxnaXZlbk5hbWU+V2Vucm9uZzwvZ2l2ZW5OYW1lPgogICAgICA8ZmFtaWx5TmFtZT5YdTwvZmFtaWx5TmFtZT4KICAgIDwvY3JlYXRvcj4KICA8L2NyZWF0b3JzPgogIDx0aXRsZXM+CiAgICA8dGl0bGU+RXhvc29tZXMgZGVyaXZlZCBmcm9tIGh1bWFuIG1lc2VuY2h5bWFsIHN0ZW0gY2VsbHMgY29uZmVyIGRydWcgcmVzaXN0YW5jZSBpbiBnYXN0cmljIGNhbmNlcjwvdGl0bGU+CiAgPC90aXRsZXM+CiAgPGRlc2NyaXB0aW9ucz4KICAgIDxkZXNjcmlwdGlvbiBkZXNjcmlwdGlvblR5cGU9IkFic3RyYWN0Ij4mbHQ7ZGl2Jmd0OyZsdDtwJmd0O01lc2VuY2h5bWFsIHN0ZW0gY2VsbHMgKE1TQ3MpIHBsYXkgYW4gaW1wb3J0YW50IHJvbGUgaW4gY2hlbW9yZXNpc3RhbmNlLiBFeG9zb21lcyBoYXZlIGJlZW4gcmVwb3J0ZWQgdG8gbW9kaWZ5IGNlbGx1bGFyIHBoZW5vdHlwZSBhbmQgZnVuY3Rpb24gYnkgbWVkaWF0aW5nIGNlbGwtY2VsbCBjb21tdW5pY2F0aW9uLiBJbiB0aGlzIHN0dWR5LCB3ZSBhaW1lZCB0byBpbnZlc3RpZ2F0ZSB3aGV0aGVyIGV4b3NvbWVzIGRlcml2ZWQgZnJvbSBNU0NzIChNU0MtZXhvc29tZXMpIGFyZSBpbnZvbHZlZCBpbiBtZWRpYXRpbmcgdGhlIHJlc2lzdGFuY2UgdG8gY2hlbW90aGVyYXB5IGluIGdhc3RyaWMgY2FuY2VyIGFuZCB0byBleHBsb3JlIHRoZSB1bmRlcmx5aW5nIG1vbGVjdWxhciBtZWNoYW5pc20uIFdlIGZvdW5kIHRoYXQgTVNDLWV4b3NvbWVzIHNpZ25pZmljYW50bHkgaW5kdWNlZCB0aGUgcmVzaXN0YW5jZSBvZiBnYXN0cmljIGNhbmNlciBjZWxscyB0byA1LWZsdW9yb3VyYWNpbCBib3RoIGluIHZpdm8gYW5kIGV4IHZpdm8uIE1TQy1leG9zb21lcyBhbnRhZ29uaXplZCA1LWZsdW9yb3VyYWNpbC1pbmR1Y2VkIGFwb3B0b3NpcyBhbmQgZW5oYW5jZWQgdGhlIGV4cHJlc3Npb24gb2YgbXVsdGktZHJ1ZyByZXNpc3RhbmNlIGFzc29jaWF0ZWQgcHJvdGVpbnMsIGluY2x1ZGluZyBNRFIsIE1SUCBhbmQgTFJQLiBNZWNoYW5pc3RpY2FsbHksIE1TQy1leG9zb21lcyB0cmlnZ2VyZWQgdGhlIGFjdGl2YXRpb24gb2YgY2FsY2l1bS9jYWxtb2R1bGluLWRlcGVuZGVudCBwcm90ZWluIGtpbmFzZXMgKENhTS1LcykgYW5kIFJhZi9NRUsvRVJLIGtpbmFzZSBjYXNjYWRlIGluIGdhc3RyaWMgY2FuY2VyIGNlbGxzLiBCbG9ja2luZyB0aGUgQ2FNLUtzL1JhZi9NRUsvRVJLIHBhdGh3YXkgaW5oaWJpdGVkIHRoZSBwcm9tb3Rpbmcgcm9sZSBvZiBNU0MtZXhvc29tZXMgaW4gY2hlbW9yZXNpc3RhbmNlLiBDb2xsZWN0aXZlbHksIE1TQy1leG9zb21lcyBjb3VsZCBpbmR1Y2UgZHJ1ZyByZXNpc3RhbmNlIGluIGdhc3RyaWMgY2FuY2VyIGNlbGxzIGJ5IGFjdGl2YXRpbmcgQ2FNLUtzL1JhZi9NRUsvRVJLIHBhdGh3YXkuIE91ciBmaW5kaW5ncyBzdWdnZXN0IHRoYXQgTVNDLWV4b3NvbWVzIGhhdmUgcHJvZm91bmQgZWZmZWN0cyBvbiBtb2RpZnlpbmcgZ2FzdHJpYyBjYW5jZXIgY2VsbHMgaW4gdGhlIGRldmVsb3BtZW50IG9mIGRydWcgcmVzaXN0YW5jZS4gVGFyZ2V0aW5nIHRoZSBpbnRlcmFjdGlvbiBiZXR3ZWVuIE1TQy1leG9zb21lcyBhbmQgY2FuY2VyIGNlbGxzIG1heSBoZWxwIGltcHJvdmUgdGhlIGVmZmljYWN5IG9mIGNoZW1vdGhlcmFweSBpbiBnYXN0cmljIGNhbmNlci4mbHQ7L3AmZ3Q7Jmx0Oy9kaXYmZ3Q7PC9kZXNjcmlwdGlvbj4KICA8L2Rlc2NyaXB0aW9ucz4KICA8c3ViamVjdHM+CiAgICA8c3ViamVjdD5JbmZlY3Rpb3VzIERpc2Vhc2VzPC9zdWJqZWN0PgogICAgPHN1YmplY3Q+SGVtYXRvbG9neTwvc3ViamVjdD4KICAgIDxzdWJqZWN0PkNhbmNlcjwvc3ViamVjdD4KICAgIDxzdWJqZWN0PkRldmVsb3BtZW50YWwgQmlvbG9neTwvc3ViamVjdD4KICAgIDxzdWJqZWN0PkJpb2xvZ2ljYWwgU2NpZW5jZXM8L3N1YmplY3Q+CiAgICA8c3ViamVjdD5DaGVtaXN0cnk8L3N1YmplY3Q+CiAgICA8c3ViamVjdD5CaW90ZWNobm9sb2d5PC9zdWJqZWN0PgogICAgPHN1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