oncotomskСибирский онкологический журналSiberian journal of oncology1814-48612312-3168Tomsk National Research Medical Сепtеr of the Russian Academy of Sciences10.21294/1814-4861-2016-15-6-48-54oncotomsk-446Research ArticleЛАБОРАТОРНЫЕ И ЭКСПЕРИМЕНТАЛЬНЫЕ ИССЛЕДОВАНИЯLABORATORY AND EXPERIMENTAL STUDIESЭКСПРЕССИЯ ГЕНОВ ЦИТОКИНОВ, АССОЦИИРОВАННЫХ С ОПУХОЛЕВЫМИ И ПРЕМЕТАСТАТИЧЕСКИМИ НИШАМИ, В СТРОМЕ РАКА МОЛОЧНОЙ ЖЕЛЕЗЫCYTOKINE GENE EXPRESSION ASSOCIATED WITH TUMOR AND PREMETASTATIC NICHES IN BREAST CANCER STROMAТаширеваЛ. А.TashirevaL. A.

Таширева Любовь Александровна - кандидат медицинских наук, научный сотрудник отделения патологической анатомии и цитологии.

634009, г. Томск, пер. Кооперативный, 5. E-mail: tashireva@oncology.tomsk.ru. SPIN-код: 4371-5340

Tashireva Liubov A. - MD, PhD, Researcher, Department of Pathological Anatomy and Cytology.

5, Kooperativny Street, 634009-Tomsk, Russia. E-mail: tashireva@oncology.tomsk.ru. SPIN-code: 4371-5340

tashireva@oncology.tomsk.ruГеращенкоТ. С.GeraschenkoT. S.

Геращенко Татьяна Сергеевна - младший научный сотрудник лаборатории молекулярной онкологии и иммунологии.

634009, г. Томск, пер. Кооперативный, 5. E-mail: t_gerashenko@list.ru SPIN-код: 7900-9700

Gerashchenko Tatiana S. - MD, Junior Researcher, Laboratory of Molecular Oncology and Immunology.

5, Kooperativny Street, 634009-Tomsk, Russia. E-mail: t_gerashenko@list.ru SPIN-code: 7900-9700

t_gerashenko@list.ruЗавьяловаМ. В.ZavyalovaM. V.

Завьялова Марина Викторовна - доктор медицинских наук, профессор, заведующая кафедрой патологической анатомии, СГМУ; ведущий научный сотрудник отделения патологической анатомии и цитологии, НИИО, ТНИМЦ РАН.

634009, г. Томск, пер. Кооперативный, 5. E-mail: zavyalovamv@mail.ru. SPIN-код: 1229-0323

Zavyalova Marina V. - MD, DSc, Professor, Head of the Department of Pathological Anatomy, SSMU; Leading Researcher, Department of Pathological Anatomy and Cytology, CRI, TNRMC, RAS.

5, Kooperativny Street, 634009-Tomsk, Russia. E-mail: zavyalovamv@mail.ru. SPIN-code: 1229-0323

zavyalovamv@mail.ruСавельеваО. Е.SavelevaO. E.

Савельева Ольга Евгеньевна - доктор медицинских наук, старший научный сотрудник отделения патологической анатомии и цитологии.

634009, г. Томск, пер. Кооперативный, 5. E-mail: olga_chechina@mail.ru. SPIN-код: 9633-9449

Savelyeva Olga E. - MD, DSc, Senior Researcher, Department of Pathological Anatomy and Cytology.

5, Kooperativny Street, 634009-Tomsk, Russia. E-mail: olga_chechina@mail.ru. SPINcode: 9633-9449

olga_chechina@mail.ruКайгородоваЕ. В.KaygorodovaE. V.

Кайгородова Евгения Викторовна - доктор медицинских наук, ведущий научный сотрудник отделения патологической анатомии и цитологии.

634009, г. Томск, пер. Кооперативный, 5. E-mail: zlobinae@mail.ru. SPIN-код: 8286-375

Kaygorodova Evgeniya V. - MD, DSc, Leading Researcher, Department of Pathological Anatomy and Cytology.

5, Kooperativny Street, 634009-Tomsk, Russia. E-mail: zlobinae@ mail.ru. SPIN-code: 8286-3757

zlobinae@mail.ruТарабановскаяН. А.TarabanovskayaN. A.

Тарабановская Наталья Анатольевна - кандидат медицинских наук, младший научный сотрудник, врач-онколог отделения общей онкологии.

634009, г. Томск, пер. Кооперативный, 5. E-mail: tarabanovskaya@inbox.ru. SPIN-код: 7481-2159

Tarabanovskaya Nataliya A. - MD, PhD, Junior Researcher, oncologist, Department of General Oncology.

5, Kooperativny Street, 634009-Tomsk, Russia. E-mail: tarabanovskaya@inbox. ru. SPINcode: 7481-2159

tarabanovskaya@inbox.ruСлонимскаяЕ. М.SlonimskayaE. M.

Слонимская Елена Михайловна - доктор медицинских наук, заведующая отделением общей онкологии, научноисследовательский институт онкологии, ТНИМЦ РАН; профессор кафедры онкологии, СГМУ.

634009, г. Томск, пер. Кооперативный, 5. E-mail: slonimskaya@rambler.ru. SPIN-код: 7763-6417

Slonimskaya Elena M. - MD, Dsc, Professor, Head of General Oncology Department, TCRI, TNRMC, RAS; Department of Oncology, SSMU.

5, Kooperativny Street, 634009-Tomsk, Russia. E-mail: slonimskaya@rambler.ru. SPIN-code: 7763-6417

slonimskaya@rambler.ruДенисовЕ. В.DenisovE. V.

Денисов Евгений Владимирович - кандидат биологических наук, старший научный сотрудник лаборатории молекулярной онкологии и иммунологии.

634009, г. Томск, пер. Кооперативный, 5. E-mail: dnsv.ev.@gmail.com. SPIN-код: 9498-5797

Denisov Evgeny V. - PhD, Senior Researcher, Laboratory of Molecular Oncology and Immunology.

5, Kooperativny Street, 634009-Tomsk, Russia. E-mail: dnsv.ev.@gmail.com. SPIN-code: 9498-5797

dnsv.ev@gmail.comПерельмутерВ. М.PerelmuterV. M.

Перельмутер Владимир Михайлович - доктор медицинских наук, профессор, заведующий отделением патологической анатомии и цитологии наук.

634009, г. Томск, пер. Кооперативный, 5. E-mail: pvm@ngs.ru. SPIN-код: 6252-5319

Perelmuter Vladimir M. - MD, DSc, Professor, Head of the Department of Pathological Anatomy and Cytology.

5, Kooperativny Street, 634009-Tomsk, Russia. E-mail: pvm@ngs. ru. SPIN-code: 6252-5319

pvm@ngs.ruНаучно-исследовательский институт онкологии, Томский национальный исследовательский медицинский центр Российской академии наукРоссияCancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of SciencesRussian FederationНаучно-исследовательский институт онкологии, Томский национальный исследовательский медицинский центр Российской академии наук; Сибирский государственный медицинский университетРоссияCancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of Sciences; Siberian State Medical UniversityRussian FederationНаучно-исследовательский институт онкологии, Томский национальный исследовательский медицинский центр Российской академии наук; Сибирский государственный медицинский университетРоссияCancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of SciencesRussian FederationСибирский государственный медицинский университет; Национальный исследовательский Томский государственный университетРоссияCancer Research Institute, Tomsk National Research Medical Center of the Russian Academy of SciencesRussian Federation2016291220161564854Copyright © Таширева Л.А., Геращенко Т.С., Завьялова М.В., Савельева О.Е., Кайгородова Е.В., Тарабановская Н.А., Слонимская Е.М., Денисов Е.В., Перельмутер В.М., 20162016Таширева Л.А., Геращенко Т.С., Завьялова М.В., Савельева О.Е., Кайгородова Е.В., Тарабановская Н.А., Слонимская Е.М., Денисов Е.В., Перельмутер В.М.Tashireva L.A., Geraschenko T.S., Zavyalova M.V., Saveleva O.E., Kaygorodova E.V., Tarabanovskaya N.A., Slonimskaya E.M., Denisov E.V., Perelmuter V.M.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/446

The tumor niche in the microenvironment of the primary tumor is believed to reflect events occurring in the premetastatic niche. In our study, based on the assessment of the expression of cytokine genes associated with inflammation and invasive and metastatic phenotype of tumor cells in the tumor microenvironment, their contribution to the creation of favorable conditions for the development of tumor and metastases was described. Material and methods. The main clinical and pathological parameters in 12 patients with invasive breast carcinoma of non-specific type (IC NST) were studied. The expression of 13 genes encoding key cytokines and chemokines in the stroma of IC NST was assessed using the PALM laser microdissection system and real-time polymerase chain reaction. Results. A direct correlation between the size of the primary tumor and the expression levels of IL1b and CXCL8 genes was found. Furthermore, it was shown that the proliferative activity of tumor cells was inversely correlated with the expression CCL2 gene that attracted monocytes. The expression of IL6 and IL8 genes involves the differentiation of monocytes into M2 macrophages, which can stimulate tumor cell invasiveness. However, microenvironment cells were found not to express MST1, FGF7, EGF genes, protein products of which provide invasive and metastatic progression of tumor cells. In our study, no significant differences in gene expression levels between patients with and without lymph node metastases were found. Nevertheless, the use of the multivariate data analysis allowed us to reveal a close relationship between the studied parameters related to a high risk of lymph node metastasis. Conclusion. A wide range of cytokines involved in the development of inflammation, recruitment of monocytes, as well as secretion of factors promoting both tumor growth and lymphatic metastasis was identified. Similar events in premetastatic niche might contribute to the development macrometastasis.

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