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Tumor-associated mesenchymal stem cells in chemically-induced breast cancer in Wistar rats

https://doi.org/10.21294/1814-4861-2019-18-1-56-64

Abstract

Objective: to compare the morphological and functional properties of mesenchymal stem cells from mammary tissues and chemically-induced mammary tumor tissues. material and methods. The study included 25 female Wistar rats. In 20 rats, mammary carcinoma was induced by intramammary injection of N-methyl-N-nitrosourea after estrus synchronization with chorionic gonadotropin. The control group consisted of 5 rats. Mammary carcinoma was verified histologically and immunohistochemically. To examine, whether the cells isolated from normal tissue and tumor tissue belonged to mesenchymal stem cells, FACS Canto II flow cytofluorometer was used. The functional properties of mesenchymal stem cells were evaluated in MTT assay by the level of nitric oxide production in normal and by hydrogen peroxide-induced hypoxia. The levels of prolactin, luteinizing hormone and estradiol E2 in urine were studied using solid-phase enzyme-linked immunosorbent assay. results. Chemically-induced mammary tumor according to histological and immunohistochemical studies corresponded to luminal B type breast cancer in humans. In rats that developed mammary tumors, the urine prolactin levels after synchronization of estrus were increased. In rats that did not develop tumors, the levels of prolactin and luteinizing hormone were decreased, but the levels of estradiol E2 were increased. More mesenchymal stem cells with CD45-/CD90+phenotype were obtained from the breast tumor tissue. Mesenchymal stem cells from tumor tissue showed increased proliferative potential and were more resistant to hypoxia. conclusion. Tumor- associated mesenchymal stem cells having high proliferative potential and resistance to hypoxia were obtained from chemically-induced mammary tumor tissue. Morphologic and functional differences in mesenchymal stem cells obtained from mammary breast tissue and tumor tissue require further studies.

About the Authors

A. P. Lykov
Research Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics. Siberian Branch of Russian Academy of Sciences; Research Institute of Circulation Pathology, Ministry of Health Care of Russian Federation
Russian Federation

Alexander P. Lykov, MD, PhD, Leading Researcher, Laboratory of Cellular Technologies; Stuff Researcher, Cellular Technologies Laboratory.
Author ID (Scopus): 7005078323. Researcher ID (WOS): I‐1999‐2018.

2, Timakova Street, 630060-Novosibirsk;
15, Rechkunovskaya Street, 630055-Novosibirsk



A. V. Kabakov
Research Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics. Siberian Branch of Russian Academy of Sciences
Russian Federation

Alexei V. Kabakov, MD, Researcher, Laboratory of Protective System Physiology.
Author ID (Scopus): 57190570129. Researcher ID (WOS): J‐3271‐2018.

2, Timakova Street, 630060-Novosibirsk



N. A. Bondarenko
Research Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics. Siberian Branch of Russian Academy of Sciences; Research Institute of Circulation Pathology, Ministry of Health Care of Russian Federation
Russian Federation

Nataliya A. Bondarenko, PhD, Researcher, Laboratory of Cellular Technologies; Stuff Researcher, Cellular Technologies Laboratory.
Author ID (Scopus): 16424587900. Researcher ID (WOS): I‐2000‐2018.

2, Timakova Street, 630060-Novosibirsk;
15, Rechkunovskaya Street, 630055-Novosibirsk



O. V. Poveshchenko
Research Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics. Siberian Branch of Russian Academy of Sciences; Research Institute of Circulation Pathology, Ministry of Health Care of Russian Federation
Russian Federation

Olga V. Poveshchenko, MD, DSc, Head of Laboratory of Cellular Technologies; Head of Laboratory, Cellular Technologies Laboratory.
Author ID (Scopus): 6505824790. Researcher ID (WOS): J‐3328‐2018.

2, Timakova Street, 630060-Novosibirsk;
15, Rechkunovskaya Street, 630055-Novosibirsk



T. V. Rayter
Research Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics. Siberian Branch of Russian Academy of Sciences
Russian Federation

Tatjana V. Raiter, Researcher, Laboratory of Protective System Physiology.
Author ID (Scopus): 57190571932.

2, Timakova Street, 630060-Novosibirsk



O. V. Kazakov
Research Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics. Siberian Branch of Russian Academy of Sciences
Russian Federation

Oleg V. Kazakov, MD, PhD, Senior Researcher, Laboratory of Protective System Physiology.
Author ID (Scopus): 57192956902. Researcher ID (WOS): J‐3282‐2018.

2, Timakova Street, 630060-Novosibirsk



D. N. Strunkin
Research Institute of Circulation Pathology, Ministry of Health Care of Russian Federation
Russian Federation

Dimitri N. Strunkin, MD, Oncologist.
Author ID (Scopus): 12800338500.

15, Rechkunovskaya Street, 630055-Novosibirsk



M. A. Surovtseva
Research Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics. Siberian Branch of Russian Academy of Sciences; Research Institute of Circulation Pathology, Ministry of Health Care of Russian Federation
Russian Federation

Maria A. Surovtseva, MD, PhD, Senior Researcher, Laboratory of Cellular Technologies; Stuff Researcher, Cellular Technologies Laboratory.
Author ID (Scopus): 35075192200. Researcher ID (WOS): J‐3408‐2018.

2, Timakova Street, 630060-Novosibirsk;
15, Rechkunovskaya Street, 630055-Novosibirsk



A. F. Poveshchenko
Research Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics. Siberian Branch of Russian Academy of Sciences; Research Institute of Circulation Pathology, Ministry of Health Care of Russian Federation; Research Institute of Fundamental and Clinical Immunology; Novosibirsk State Medical University; Novosibirsk State Pedagogic University
Russian Federation

Alexander F. Poveshchenko, MD, DSc, Head of Laboratory of Protective System Physiology; Senior Researcher, Cellular Technologies Laboratory; Teacher, Novosibirsk State Medical University; Teacher, Novosibirsk State Pedagogic University.
Author ID (Scopus): 6603573909. Researcher ID (WOS): J‐3424‐2018.

2, Timakova Street, 630060-Novosibirsk; 15, Rechkunovskaya Street, 630055-Novosibirsk; 14, Yadrintsevskaya Street, 630099-Novosibirsk; 52, Krasny prospect, 630091-Novosibirsk; 28, Vilyuiskaya Street, 630126-Novosibirsk



V. I. Konenkov
Research Institute of Clinical and Experimental Lymрhology – Branch of the Institute of Cytology and Genetics. Siberian Branch of Russian Academy of Sciences
Russian Federation

Vladimir I. Konenkov, MD, DSc, Professor, Member of the Russian Academy of Sciences.
Author ID (Scopus): 7005910476. Researcher ID (WOS): J‐6329‐2018.

2, Timakova Street, 630060-Novosibirsk



References

1. Чочиева А.Р. Исследование влияния летрозола на некоторые показатели гормонально‐метаболического статуса при эксперимен‐ тальном раке молочной железы. Сибирский онкологический журнал. 2008; 1: 100–102. [Chochieva A.R. The study of the influence of letrosole on some factors of gormonal and metabolic status under experimental carcinogenesis of the mammary gland. Siberian Journal of Oncology. 2008; 1: 100–102. (in Russian)].

2. Лыков А.П., Кабаков А.В., Казаков О.В., Бондаренко Н.А., Повещенко О.В., Райтер Т.В., Повещенко А.Ф., Стрункин Д.Н., Коненков В.И. Уровни микроРНК и гормонов в лимфе грудного протока крыс на модели рака молочной железы, индуцированной N‐метил‐N‐нитрозомочевиной. Бюллетень экспериментальной биологии и медицины. 2016; 162 (9): 374–377. [Lykov A.P., Kabakov A.V., Kazakov O.V., Bondarenko N.A., Poveshchenko O.V., Raiter T.V., Poveshchenko A.F., Strunkin D.N., Konenkov V.I. Levels of miRNAs and hormones in the lymph of the thoracic duct of rats on a model of breast cancer induced by N‐methyl‐N‐nitrosourea. Bulletin of Experimental Biology and Medicine. 2016; 162 (9): 374–377. (in Russian)].

3. Farhat G.N., Cummings S.R., Chlebowski R.T., Parimi N., Cauley J.A., Rohan T.E., Huang A.J., Vitolins M., Hubbell F.A., Manson J.E., Cochrane B.B., Lane D.S., Lee J.S. Sex hormone levels and risks of estrogen receptor‐negative and estrogen receptor‐positive breast cancers. J Natl Cancer Inst. 2011 Apr 6; 103 (7): 562–70. doi: 10.1093/jnci/djr031.

4. Al-Rakan M.A., Colak D., Hendrayani S.F., Al-Bakheet A., Al-Mohanna F.H., Kaya N., Al-Malik O., Aboussekhra A. Breast stromal fi‐ broblasts from histologically normal surgical margins are pro‐carcinogenic. J Pathol. 2013 Dec; 231 (4): 457–65. doi: 10.1002/path.4256.

5. Cuiffo B.G., Campagne A., Bell G.W., Lembo A., Orso F., Lien E.C., Bhasin M.K., Raimo M., Hanson S.E., Marusyk A., El-Ashry D., Hematti P., Polyak K., Mechta-Grigoriou F., Mariani O., Volinia S., Vincent-Salomon A., Taverna D., Karnoub A.E. MSC‐regulated microRNAs con‐ verge on the transcription factor FOXP2 and promote breast cancer metastasis. Cell Stem Cell. 2014 Dec 4; 15 (6): 762–74. doi: 10.1016/j. stem.2014.10.001.

6. Zhang C., Zhai W., Xie Y., Chen Q., Zhu W., Sun X. Mesenchymal stem cells derived from breast cancer tissue promote the proliferation and migration of the MCF‐7 cell line in vitro. Oncol Lett. 2013 Dec; 6 (6): 1577–1582.

7. El-Abd E., Matta C.A., Sheta M., El-Kerm Y., Sakr S. Histopatho‐ logical characteristics of breast cancer and evaluation of ER alpha and Her‐2neu using immunohistochemical and RT‐PCR techniques. Alexandria J Medicine. 2014; 50: 275–282.

8. Katanov C., Lerrer S., Liubomirski Y., Leider-Trejo L., Meshel T., Bar J., Feniger-Barish R., Kamer I., Soria-Artzi G., Kahani H., Banerjee D., Ben-Baruch A. Regulation of the inflammatory profile of stromal cells in human breast cancer: prominent roles for TNF‐α and the NF‐κB pathway. Stem Cell Res Ther. 2015 May 1; 6: 87. doi: 10.1186/s13287‐ 015‐0080‐7.

9. Lacerda L., Debeb B.G., Smith D., Larson R., Solley T., Xu W., Krishnamurthy S., Gong Y., Levy L.B., Buchholz T., Ueno N.T., Klopp A., Woodward W.A. Mesenchymal stem cells mediate the clinical phenotype of inflammatory breast cancer in a preclinical model. Breast Cancer Res. 2015; 17: 42. doi: 10.1186/s13058‐015‐0549‐4.

10. Usha L., Rao G., Christopherson Ii K., Xu X. Mesenchymal stem cells develop tumor tropism but do not accelerate breast cancer tumori‐ genesis in a somatic mouse breast cancer model. PLoS One. 2013 Sep 12; 8 (9): e67895. doi: 10.1371/journal.pone.0067895.

11. Zhao M., Sachs P.C., Wang X., Dumur C.I., Idowu M.O., Robila V., Francis M.P., Ware J., Beckman M., Rizki A., Holt S.E., Elmore L.W. Mesenchymal stem cells in mammary adipose tissue stimulate progres‐ sion of breast cancer resembling the basal‐type. Cancer Biol Ther. 2012 Jul; 13 (9): 782–92.


Review

For citations:


Lykov A.P., Kabakov A.V., Bondarenko N.A., Poveshchenko O.V., Rayter T.V., Kazakov O.V., Strunkin D.N., Surovtseva M.A., Poveshchenko A.F., Konenkov V.I. Tumor-associated mesenchymal stem cells in chemically-induced breast cancer in Wistar rats. Siberian journal of oncology. 2019;18(1):56-64. (In Russ.) https://doi.org/10.21294/1814-4861-2019-18-1-56-64

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ISSN 1814-4861 (Print)
ISSN 2312-3168 (Online)