<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE root>
<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="other" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Advances in Molecular Oncology</journal-id><journal-title-group><journal-title xml:lang="en">Advances in Molecular Oncology</journal-title><trans-title-group xml:lang="ru"><trans-title>Успехи молекулярной онкологии</trans-title></trans-title-group></journal-title-group><issn publication-format="print">2313-805X</issn><issn publication-format="electronic">2413-3787</issn><publisher><publisher-name xml:lang="en">Publishing House ABV Press</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">106</article-id><article-id pub-id-type="doi">10.17650/2313-805X-2017-4-3-92-98</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>RESEARCH ARTICLES</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>ЭКСПЕРИМЕНТАЛЬНЫЕ СТАТЬИ</subject></subj-group><subj-group subj-group-type="article-type"><subject></subject></subj-group></article-categories><title-group><article-title xml:lang="en">Exosomes and development of cancer cell resistance to metformin: pilot study</article-title><trans-title-group xml:lang="ru"><trans-title>Экзосомы и развитие резистентности опухолевых клеток к метформину: пилотное исследование</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Semina</surname><given-names>S. E.</given-names></name><name xml:lang="ru"><surname>Семина</surname><given-names>С. Е.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>24 Kashirskoe Shosse, Moscow 115478.</p></bio><bio xml:lang="ru"><p>115478 Москва, Каширское шоссе, 24.</p></bio><email>s.e.semina@gmail.com</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Rudenskaya</surname><given-names>E. A.</given-names></name><name xml:lang="ru"><surname>Руденская</surname><given-names>Е. А.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>24 Kashirskoe Shosse, Moscow 115478.</p></bio><bio xml:lang="ru"><p>115478 Москва, Каширское шоссе, 24.</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Mittenberg</surname><given-names>A. G.</given-names></name><name xml:lang="ru"><surname>Миттенберг</surname><given-names>А. Г.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>4 Tikhoretskiy Prospekt, Saint Petersburg 194064.</p></bio><bio xml:lang="ru"><p>194064 Санкт-Петербург, Тихорецкий проспект, 4.</p></bio><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Shabel’nikov</surname><given-names>S. V.</given-names></name><name xml:lang="ru"><surname>Шабельников</surname><given-names>С. В.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>4 Tikhoretskiy Prospekt, Saint Petersburg 194064.</p></bio><bio xml:lang="ru"><p>194064 Санкт-Петербург, Тихорецкий проспект, 4.</p></bio><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Krasil’nikov</surname><given-names>M. A.</given-names></name><name xml:lang="ru"><surname>Красильников</surname><given-names>М. А.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>24 Kashirskoe Shosse, Moscow 115478.</p></bio><bio xml:lang="ru"><p>115478 Москва, Каширское шоссе, 24.</p></bio><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Research Institute of Carcinogenesis, N.N. Blokhin National Medical Research Center of Oncology, Ministry of Health of Russia.</institution></aff><aff><institution xml:lang="ru">НИИ канцерогенеза ФГБУ «Национальный медицинский исследовательский центр онкологии им. Н.Н. Блохина»  Минздрава России.</institution></aff></aff-alternatives><aff-alternatives id="aff2"><aff><institution xml:lang="en">Institute of Cytology of the Russian Academy of Sciences.</institution></aff><aff><institution xml:lang="ru">ФГБУН «Институт цитологии Российской академии наук».</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2017-09-15" publication-format="electronic"><day>15</day><month>09</month><year>2017</year></pub-date><volume>4</volume><issue>3</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>92</fpage><lpage>98</lpage><history><date date-type="received" iso-8601-date="2017-10-16"><day>16</day><month>10</month><year>2017</year></date><date date-type="accepted" iso-8601-date="2017-10-16"><day>16</day><month>10</month><year>2017</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2017, Semina S.E., Rudenskaya E.A., Mittenberg A.G., Shabel’nikov S.V., Krasil’nikov M.A.</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2017, Семина С.Е., Руденская Е.А., Миттенберг А.Г., Шабельников С.В., Красильников М.А.</copyright-statement><copyright-year>2017</copyright-year><copyright-holder xml:lang="en">Semina S.E., Rudenskaya E.A., Mittenberg A.G., Shabel’nikov S.V., Krasil’nikov M.A.</copyright-holder><copyright-holder xml:lang="ru">Семина С.Е., Руденская Е.А., Миттенберг А.Г., Шабельников С.В., Красильников М.А.</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/"/><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://creativecommons.org/licenses/by/4.0</ali:license_ref></license></permissions><self-uri xlink:href="https://umo.abvpress.ru/jour/article/view/106">https://umo.abvpress.ru/jour/article/view/106</self-uri><abstract xml:lang="en"><p><bold>Objective</bold>: to study the role of the intercellular interactions in the progression of the cancer cells resistance to metformin, a biguanide antidiabetic drug exhibited the marked anti-tumor activity.</p><p><bold>Results</bold>. Earlier we have demonstrated the effect of horizontal transferring of hormonal resistance of breast cancer cells  from cell to cell, and showed the key role of exosomes on the transferring of the resistance. Here we have shown the effect of the horizontal transferring of metformin resistance in breast cancer cells – similar to the progression of hormonal resistance. We found that horizontal transferring of the metformin resistance is mediated via exosomes secreted by the resistant cells. The proteome analysis of the exosomes revealed several proteins differentially expressed in the exosomes of metformin-resistant cells and associated with the regulation of cell response to apoptotic drugs.</p><p><bold>Conclusions.</bold> Totally, the data presented demonstrate the new mechanism of the development of the cancer cell resistance based on the intercellular interactions, opening the new insights in the target therapy of breast cancer.</p></abstract><trans-abstract xml:lang="ru"><p/></trans-abstract><kwd-group xml:lang="en"><kwd>breast cancer</kwd><kwd>resistance</kwd><kwd>metformin</kwd><kwd>exosomes</kwd><kwd>intercellular interactions</kwd><kwd>proteome</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>рак молочной железы</kwd><kwd>резистентность</kwd><kwd>метформин</kwd><kwd>экзосомы</kwd><kwd>межклеточное взаимодействие</kwd><kwd>протеом</kwd></kwd-group><funding-group/></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><citation-alternatives><mixed-citation xml:lang="en">1. Evans J.M., Donnelly L.A., Emslie- Smith A.M. et al. Metformin and reduced risk of cancer in diabetic patients. BMJ 2005;330(7503):1304–5.</mixed-citation><mixed-citation xml:lang="ru">Evans J.M., Donnelly L.A., Emslie- Smith A.M. et al. Metformin and reduced risk of cancer in diabetic patients. BMJ 2005;330(7503):1304–5.</mixed-citation></citation-alternatives></ref><ref id="B2"><label>2.</label><citation-alternatives><mixed-citation xml:lang="en">2. Shcherbakov A.M., Andreeva O.E., Shatskaya V.A., Krasil’nikov M.A. The relationships between snail1 and estrogen receptor signaling in breast cancer cells. J Cell Biochem 2012;113(6):2147–55.</mixed-citation><mixed-citation xml:lang="ru">Shcherbakov A.M., Andreeva O.E., Shatskaya V.A., Krasil’nikov M.A. The relationships between snail1 and estrogen receptor signaling in breast cancer cells. J Cell Biochem 2012;113(6):2147–55.</mixed-citation></citation-alternatives></ref><ref id="B3"><label>3.</label><citation-alternatives><mixed-citation xml:lang="en">3. Viedma-Rodriguez R., Baiza-Gutman L., Salamanca-Gómez F. et al. Mechanisms associated with resistance to tamoxifen in estrogen receptor-positive breast cancer (review). Oncol Rep 2014;32(1):3–15.</mixed-citation><mixed-citation xml:lang="ru">Viedma-Rodriguez R., Baiza-Gutman L., Salamanca-Gómez F. et al. Mechanisms associated with resistance to tamoxifen in estrogen receptor-positive breast cancer (review). Oncol Rep 2014;32(1):3–15.</mixed-citation></citation-alternatives></ref><ref id="B4"><label>4.</label><citation-alternatives><mixed-citation xml:lang="en">4. Nalvarte I., Schwend T., Gustafsson J.A. Proteomics analysis of the estrogen receptor alpha receptosome. Mol Cell Proteomics 2010;9(7):1411–22.</mixed-citation><mixed-citation xml:lang="ru">Nalvarte I., Schwend T., Gustafsson J.A. Proteomics analysis of the estrogen receptor alpha receptosome. Mol Cell Proteomics 2010;9(7):1411–22.</mixed-citation></citation-alternatives></ref><ref id="B5"><label>5.</label><citation-alternatives><mixed-citation xml:lang="en">5. Bihani T., Ezell S.A., Ladd B. et al. Resistance to everolimus driven by epigenetic regulation of MYC in ER+ breast cancers. Oncotarget 2015;6(4):2407–20.</mixed-citation><mixed-citation xml:lang="ru">Bihani T., Ezell S.A., Ladd B. et al. Resistance to everolimus driven by epigenetic regulation of MYC in ER+ breast cancers. Oncotarget 2015;6(4):2407–20.</mixed-citation></citation-alternatives></ref><ref id="B6"><label>6.</label><citation-alternatives><mixed-citation xml:lang="en">6. Oliveras-Ferraros C., Vazquez-Martin A., Cuyàs E. et al. Acquired resistance to metformin in breast cancer cells triggers transcriptome reprogramming toward a degradome-related metastatic stem-like profile. Cell Cycle 2014;13(7):1132–44.</mixed-citation><mixed-citation xml:lang="ru">Oliveras-Ferraros C., Vazquez-Martin A., Cuyàs E. et al. Acquired resistance to metformin in breast cancer cells triggers transcriptome reprogramming toward a degradome-related metastatic stem-like profile. Cell Cycle 2014;13(7):1132–44.</mixed-citation></citation-alternatives></ref><ref id="B7"><label>7.</label><citation-alternatives><mixed-citation xml:lang="en">7. Shcherbakov A.M., Sorokin D.V., Tatar- skiy V.V. Jr et al. The phenomenon of acquired resistance to metformin in breast cancer cells: the interaction of growth pathways and estrogen receptor signaling. IUBMB Life 2016;68(4):281–92.</mixed-citation><mixed-citation xml:lang="ru">Shcherbakov A.M., Sorokin D.V., Tatar- skiy V.V. Jr et al. The phenomenon of acquired resistance to metformin in breast cancer cells: the interaction of growth pathways and estrogen receptor signaling. IUBMB Life 2016;68(4):281–92.</mixed-citation></citation-alternatives></ref><ref id="B8"><label>8.</label><citation-alternatives><mixed-citation xml:lang="en">8. Семина С.Е., Багров Д.В., Красильников М.А. Межклеточные взаимодействия и развитие гормональной резистентности клеток рака молочной железы. Успехи молекулярной онкологии 2015;2(2):50–5. [Semina S.E., Bagrov D.V., Krasil’nikov M.A. Intercellular interactions and progression of hormonal resistance of breast cancer cells. Uspekhi molekulyarnoy onkologii = Advances in Molecular Oncology 2015;2(2):50–5. (In Russ.)].</mixed-citation><mixed-citation xml:lang="ru">Семина С.Е., Багров Д.В., Красильников М.А. Межклеточные взаимодействия и развитие гормональной резистентности клеток рака молочной железы. Успехи молекулярной онкологии 2015;2(2):50–5. [Semina S.E., Bagrov D.V., Krasil’nikov M.A. Intercellular interactions and progression of hormonal resistance of breast cancer cells. Uspekhi molekulyarnoy onkologii = Advances in Molecular Oncology 2015;2(2):50–5. (In Russ.)].</mixed-citation></citation-alternatives></ref><ref id="B9"><label>9.</label><citation-alternatives><mixed-citation xml:lang="en">9. Reid G., Hübner M.R., Métivier R. et al. Cyclic, proteasome-mediated turnover of unliganded and liganded ERalpha on responsive promoters is an integral feature of estrogen signaling. Mol Cell 2003;11(3):695–707.</mixed-citation><mixed-citation xml:lang="ru">Reid G., Hübner M.R., Métivier R. et al. Cyclic, proteasome-mediated turnover of unliganded and liganded ERalpha on responsive promoters is an integral feature of estrogen signaling. Mol Cell 2003;11(3):695–707.</mixed-citation></citation-alternatives></ref><ref id="B10"><label>10.</label><citation-alternatives><mixed-citation xml:lang="en">10. Thery C., Amigorena S., Raposo G., Clayton A. Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr Protoc Cell Biol 2006. Chapter 3: Unit 3.22.</mixed-citation><mixed-citation xml:lang="ru">Thery C., Amigorena S., Raposo G., Clayton A. Isolation and characterization of exosomes from cell culture supernatants and biological fluids. Curr Protoc Cell Biol 2006. Chapter 3: Unit 3.22.</mixed-citation></citation-alternatives></ref><ref id="B11"><label>11.</label><citation-alternatives><mixed-citation xml:lang="en">11. Yang B., Wang S., Yu S. et al. C1q/tumor necrosis factor-related protein 3 inhibits oxidative stress during intracerebral hemorrhage via PKA signaling. Brain Res 2017;1657:176–84.</mixed-citation><mixed-citation xml:lang="ru">Yang B., Wang S., Yu S. et al. C1q/tumor necrosis factor-related protein 3 inhibits oxidative stress during intracerebral hemorrhage via PKA signaling. Brain Res 2017;1657:176–84.</mixed-citation></citation-alternatives></ref><ref id="B12"><label>12.</label><citation-alternatives><mixed-citation xml:lang="en">12. Choi J., Kim D.I., Kim J. et al. Hornerin is involved in breast cancer progression. J Breast Cancer 2016;19(2): 142–7.</mixed-citation><mixed-citation xml:lang="ru">Choi J., Kim D.I., Kim J. et al. Hornerin is involved in breast cancer progression. J Breast Cancer 2016;19(2): 142–7.</mixed-citation></citation-alternatives></ref><ref id="B13"><label>13.</label><citation-alternatives><mixed-citation xml:lang="en">13. Wang Z.C., E D., Batu D.L. et al. 2DDIGE proteomic analysis of changes in estrogen/progesterone-induced rat breast hyperplasia upon treatment with the Mongolian remedy RuXian-I. Molecules 2011;16(4):3048–65.</mixed-citation><mixed-citation xml:lang="ru">Wang Z.C., E D., Batu D.L. et al. 2DDIGE proteomic analysis of changes in estrogen/progesterone-induced rat breast hyperplasia upon treatment with the Mongolian remedy RuXian-I. Molecules 2011;16(4):3048–65.</mixed-citation></citation-alternatives></ref><ref id="B14"><label>14.</label><citation-alternatives><mixed-citation xml:lang="en">14. Queiroz E.A., Puukila S., Eichler R. et al. Metformin induces apoptosis and cell cycle arrest mediated by oxidative stress, AMPK and FOXO3a in MCF-7 breast cancer cells. PLoS One 2014;9(5): e98207</mixed-citation><mixed-citation xml:lang="ru">Queiroz E.A., Puukila S., Eichler R. et al. Metformin induces apoptosis and cell cycle arrest mediated by oxidative stress, AMPK and FOXO3a in MCF-7 breast cancer cells. PLoS One 2014;9(5): e98207</mixed-citation></citation-alternatives></ref></ref-list></back></article>
