oncotomskСибирский онкологический журналSiberian journal of oncology1814-48612312-3168Tomsk National Research Medical Сепtеr of the Russian Academy of Sciences10.21294/1814-4861-2022-21-6-68-80oncotomsk-2376Research ArticleЛАБОРАТОРНЫЕ И ЭКСПЕРИМЕНТАЛЬНЫЕ ИССЛЕДОВАНИЯLABORATORY AND EXPERIMENTAL STUDIESИзменение функционального профиля моноцитов крови при раке молочной железыChanges in blood monocyte functional profile in breast cancerhttps://orcid.org/0000-0002-5121-2535ФедоровА. А.FedorovA. A.

 

Федоров Антон Андреевич, младший научный сотрудник лаборатории биологии опухолевой прогрессии, 

634009, г. Томск, пер. Кооперативный, 5

Anton A. Fedorov, Junior Researcher, Laboratory of Cancer Progression Biology, 

5, Kooperativny St., 634009, Tomsk

 

https://orcid.org/0000-0002-5121-2535ПростакишинаЕ. А.ProstakishinaE. A.

Федоров Антон Андреевич, младший научный сотрудник лаборатории биологии опухолевой прогрессии, 

634050, г. Томск, ул. Ленина, 36

Elizaveta A. Prostakishina, Laboratory assistant, Laboratory of Translational Cellular and Molecular Biomedicine,

36, Lenina St., 634050, Tomsk

https://orcid.org/0000-0002-5121-2535ПатышеваМ. Р.PatyshevaM. R.

Федоров Антон Андреевич, младший научный сотрудник лаборатории биологии опухолевой прогрессии, 634009, г. Томск, пер. Кооперативный, 5;

634050, г. Томск, ул. Ленина, 36

Marina R. Patysheva, Junior Researcher, Laboratory of Cancer Progression Biology, 5, Kooperativny St., 634009, Tomsk;

Junior Researcher, Laboratory of Translational Cellular and Molecular Biomedicine, 36, Lenina St., 634050, Tomsk

patysheva_mr@onco.tnimc.ruhttps://orcid.org/0000-0003-3297-1680ФроловаА. А.FrolovaA. A.

Фролова Анастасия Алексеевна, лаборант-исследователь лаборатории иммунологии и молекулярной онкологии, 634009, г. Томск, пер. Кооперативный, 5;

лаборант лаборатории трансляционной клеточной и молекулярной биомедицины, 634050, г. Томск, ул. Ленина, 36

Anastasia A. Frolova, Laboratory assistant, Laboratory of Immunology and Molecular Oncology, 5, Kooperativny St., 634009, Tomsk;

Laboratory Assistant, Laboratory of Translational Cellular and Molecular Biomedicine, 36, Lenina St., 634050, Tomsk

https://orcid.org/0000-0002-0646-6093ЯмщиковП. С.IamshchikovP. S.

Ямщиков Павел Сергеевич, биоинформатик, лаборатория биологии опухолевой прогрессии, 634009, г. Томск, пер. Кооперативный, 5;

лаборант лаборатории трансляционной клеточной и молекулярной биомедицины, 634050, г. Томск, ул. Ленина, 36

Pavel S. Iamshikov, Bioinformatician, Laboratory of Cancer Progression Biology, 5, Kooperativny St., 634009, Tomsk;

Laboratory Assistant, Laboratory of Translational Cellular and Molecular Biomedicine, 36, Lenina St., 634050, Tomsk

https://orcid.org/0000-0001-5758-7330ЛарионоваИ. В.LarionovaI. V.

Ларионова Ирина Валерьевна, кандидат медицинских наук, старший научный сотрудник, 634009, г. Томск, пер. Кооперативный, 5;

старший научный сотрудник лаборатории трансляционной клеточной и молекулярной биомедицины, 634050, г. Томск, ул. Ленина, 36

Irina V. Larionova, MD, PhD, Senior Researcher, 5, Kooperativny St., 634009, Tomsk;

Senior Researcher of Laboratory of Translational Cellular and Molecular Biomedicine, 36, Lenina St., 634050, Tomsk

https://orcid.org/0000-0003-0601-2240СтахееваМ. Н.StakheyevaM. N.

Стахеева Марина Николаевна, доктор медицинских наук, ведущий научный сотрудник лаборатории молекулярной онкологии и иммунологии, 

634009, г. Томск, пер. Кооперативный, 5

Marina N. Stakheyeva, MD, DSc, Leading Researcher of the Laboratory of Molecular Oncology and Immunology,

5, Kooperativny St., 634009, Tomsk

https://orcid.org/0000-0003-3013-9858ДорофееваМ. С.DorofeevaM. S.

Дорофеева Мария Сергеевна, лаборант-исследователь лаборатории трансляционной клеточной и молекулярной биомедицины, 

634050, г. Томск, ул. Ленина, 36

Maria S. Dorofeeva, Laboratory Assistant, Laboratory of Translational Cellular and Molecular Biomedicine,

36, Lenina St., 634050, Tomsk

https://orcid.org/0000-0001-5281-7758БрагинаО. Д.BraginaO. D.

Брагина Ольга Дмитриевна, доктор медицинских наук, старший научный сотрудник отделения радионуклидной диагностики,

634009, г. Томск, пер. Кооперативный, 5

Olga D. Bragina, MD, DSc, Senior Researcher, Nuclear Medicine Department, 

5, Kooperativny St., 634009, Tomsk

https://orcid.org/0000-0002-3651-0665ЧойнзоновЕ. Л.ChoynzonovE. L.

Чойнзонов Евгений Лхамацыренович, доктор медицинских наук, профессор, академик РАН, директор, 

634009, г. Томск, пер. Кооперативный, 5

Evgeny L. Choynzonov, MD, DSc, Professor, Member of the Russian Academy of Sciences, 

5, Kooperativny St., 634009, Tomsk

https://orcid.org/0000-0003-0898-3075КжышковскаЮ. Г.KzhyshkowskaJ. G.

Кжышковска Юлия Георгиевна, доктор биологических наук, профессор, заведующая лабораторией трансляционной клеточной и молекулярной биомедицины, 

634050, г. Томск, ул. Ленина, 36

Julia G. Kzhyshkowska, DSc, Professor, Head of the Laboratory of Translational Cellular and Molecular Biomedicine,

36, Lenina St., 634050, Tomsk

https://orcid.org/0000-0003-1526-9013ЧердынцеваН. В.CherdyntsevaN. V.

Чердынцева Надежда Викторовна, доктор биологических наук, профессор, член-корреспондент РАН, заведующая лабораторией молекулярной онкологии и иммунологии, 634009, г. Томск, пер. Кооперативный, 5;

ведущий научный сотрудник, 634050, г. Томск, ул. Ленина, 36

Nadezhda V. Cherdyntseva, DSc, Professor, Corresponding Member of Russian Academy of Sciences, Head of the Laboratory of Molecular Oncology and Immunology, 5, Kooperativny St., 634009, Tomsk;

Senior Researcher of Laboratory of Translational Cellular and Molecular Biomedicine, 36, Lenina St., 634050, Tomsk

Научно-исследовательский институт онкологии, Томский национальный исследовательский медицинский центр Российской академии наукРоссияCancer Research Institute, Тomsk National Research Medical Center, Russian Academy of SciencesRussian FederationФГАОУ ВО «Национальный исследовательский Томский государственный университет»РоссияNational Research Tomsk State UniversityRussian FederationНаучно-исследовательский институт онкологии, Томский национальный исследовательский медицинский центр Российской академии наук; ФГАОУ ВО «Национальный исследовательский Томский государственный университет»РоссияCancer Research Institute, Тomsk National Research Medical Center, Russian Academy of Sciences; National Research Tomsk State UniversityRussian Federation2022311220222166880Copyright © Федоров А.А., Простакишина Е.А., Патышева М.Р., Фролова А.А., Ямщиков П.С., Ларионова И.В., Стахеева М.Н., Дорофеева М.С., Брагина О.Д., Чойнзонов Е.Л., Кжышковска Ю.Г., Чердынцева Н.В., 20232023Федоров А.А., Простакишина Е.А., Патышева М.Р., Фролова А.А., Ямщиков П.С., Ларионова И.В., Стахеева М.Н., Дорофеева М.С., Брагина О.Д., Чойнзонов Е.Л., Кжышковска Ю.Г., Чердынцева Н.В.Fedorov A.A., Prostakishina E.A., Patysheva M.R., Frolova A.A., Iamshchikov P.S., Larionova I.V., Stakheyeva M.N., Dorofeeva M.S., Bragina O.D., Choynzonov E.L., Kzhyshkowska J.G., Cherdyntseva N.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.siboncoj.ru/jour/article/view/2376

Цель исследования ‒ оценить особенности функционального профиля моноцитов периферической крови у больных неметастатической формой рака молочной железы.

Материал и методы

Материал и методы. В исследование вошли 10 больных раком молочной железы II–III стадии (T1–3N0–2M0). В качестве контроля была обследована группа из 7 здоровых женщин. Моноциты были получены из периферической крови путем сортировки популяций с фенотипом CD14+16-, CD14+16+ и CD14-16+. Проведено полнотранскриптомное профилирование полученных моноцитов от больных раком молочной железы и здоровых женщин. Из полученных моноцитов in vitro были дифференцированы макрофаги. Проведена оценка способности полученных от макрофагов кондиционных сред влиять на апоптоз и пролиферацию клеток линии MDA-MB 231.

Результаты

Результаты. Показано, что транскриптомный профиль моноцитов больных РЖЖ имеет выраженные отличия по сравнению со здоровыми женщинами. Моноциты пациенток с раком молочной железы отличаются повышенной экспрессией мРНК белков-транспортеров ABCA1, ABCG1; хемокинов CCR1, CRRL2, CXCR4; факторов созревания и дифференцировки моноцитов Mafb и Jun; факторов, опосредующих эндоцитоз CD163, Siglec1; протеаз и тетраспонинов ADAM9, CD151, CD82 и ростового фактора HBEGF. Макрофаги, полученные в результате культивирования моноцитов больных раком молочной железы в условиях in vitro, продуцировали факторы, которые позволили поддерживать пролиферацию клеточной линии опухолевых клеток, чего не наблюдалось для моноцитов здоровых доноров.

Заключение

Заключение. Опухоль молочной железы оказывает системное влияние на моноциты периферической крови, программируя их к дифференцировке в макрофаги с проопухолевой функциональной активностью. 

The purpose of the study was to identify functional features of circulation monocytes in patients with nonmetastatic breast cancer.

Material and Methods

Material and Methods. The study cohort consisted of 10 breast cancer patients treated at Tomsk Cancer Research Institute. 7 healthy female volunteers were enrolled as a control group. CD14+16-, CD14+16+ and CD14-16+ monocytes subsets were obtained from blood by sorting. Whole transcriptome profling was provided in monocytes from patients and healthy females. Macrophages were differentiated from the obtained monocytes under in vitro conditions. The ability of conditioned media obtained from macrophages to infuence apoptosis and proliferation of MDA-MB 231 cell line was evaluated.

Results

Results. Transcriptomic profling revealed signifcant changes in monocytes of breast cancer patients. CD14+16- subset showed higher expression of transporters ABCA1 and ABCG1; chemokines CCR1, CRRL2, CXCR4; maturation and differentiation factors Mafb and Jun; endocytosis mediating factors CD163 and Siglec1; proteases and tetrasponins ADAM9, CD151, CD82, and growth factor HBEGF in patient group. Macrophages derived from monocytes of breast cancer patients produced factors that supported proliferation of the MDA-MB 231 cell line, which was not observed for monocytes from healthy volunteers.

Conclusion

Conclusion. Thus, breast carcinoma has a systemic effect on peripheral blood monocytes, programming them to differentiate into macrophages with tumor supporting capacity. 

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The authors declare that there are no conflicts of interest present.