Email this article IMMUNO-HORMONAL REGULATION OF TUMOR PROLIFERATION IN BREAST CANCER PATIENTS
- Authors: Glushkov A.1, Polenok E.2, Gordeeva L.1, Antonov A.3, Bayramov P.3, Verzhbitskaya N.3, Kolpinskiy G.4,5
-
Affiliations:
- Institute of Human Ecology, Federal Research Center of Coal and Coal chemistry SB RAS
- Institute of Human Ecology Federal Research Center of Coal and Coal chemistry SB RAS
- Kuzbass Clinical Oncology Dispensary
- Kemerovo State Medical University
- Kemerovo Clinical Diagnostic Сenter
- Section: ORIGINAL ARTICLES
- URL: https://rusimmun.ru/jour/article/view/13990
- DOI: https://doi.org/10.46235/1028-7221-13990-IRO
- ID: 13990
Cite item
Full Text
Abstract
Abstract
It is well known that tumor cells proliferation is regulated by sex steroid hormones, estradiol and progesterone (E2 and Pg) in breast cancer patients (BCP). Apart from that auto-antibodies specific to estrogen receptor (ERα) were detected in the blood serum of BCP. Their levels positively correlated with the percentage of Ki-67 expressing breast cancer cells. We proposed that antiidiotypic auto-antibodies to E2 and Pg (IgG2-E2 and IgG2-Pg) could act as antibodies against membrane ER and progesterone receptor (PR). Our study aimed for research of IgG2-E2 and IgG2-Pg according to E2 and Pg serum levels in association with Ki-67 positive tumors in BCP. Antiidiotypic antibodies were studied in ER+BCP (374 – I stage and 379 – II–IV stages) using ELISA technique with monoclonal antibodies against E2 and Pg as adsorbed antigens. Blood serum concentrations of E2 and Pg measured using “ImmunoEA-Estradiol” and “ImmunoEA-Progesterone” test-sistems (“Immunotech”, Moscow). Tumor Ki-67 was studied by standart immunohistochemical technique in Kemerovo oncological hospital. The high percentage of Ki-67 positive breast cancer cells (Ki-67>30) was higher in BCP II–IV stages than in I stage (50.7% vs 29.8%, p<0,001). Such raise were detected for the BCP with low levels of both IgG2-E2 and IgG2-Pg: 1) at the low serum concentration E2≤200 pmol/L (50.9% vs 21.3%, р<0.001); 2) at the high E2>200 pmol/L (74.2% vs 34.1%, р = 0.003); 3) at the low Pg≤600 pmol/L (60.6% vs 22.2%, р<0.001); 4) at the high Pg>600 pmol/L (58.5% vs 30.8%, р = 0.02). There were not revealed the same differences between II–IV and I stages BCP with low levels of both IgG2-E2 and IgG2-Pg. Corresponding Ki-67>30 indicators were: 1) 36.9% vs 22.0% (р = 0.14); 2) 48.4% vs 34.5% (р = 0.08); 3) 34.0% vs 27.7% (р = 0.75). The statistically significant differences were detected in BCP with Pg>600 pmol/L and high IgG2-E2 and IgG2-Pg levels only: 48.1% vs 26.6%, (р = 0.01). So antiidiotypic auto-antibodies to steroid hormones take part in regulation of tumor proliferation in BCP. Immunoassay of IgG2-E2 and IgG2-Pg may be used for prognosis of tumor proliferation at the growing breast cancer.
Keywords
About the authors
Andrey Glushkov
Institute of Human Ecology, Federal Research Center of Coal and Coal chemistry SB RAS
Author for correspondence.
Email: glushkovan@ihe.sbras.ru
ORCID iD: 0000-0002-8560-6719
SPIN-code: 9536-8530
Scopus Author ID: 7006323832
ResearcherId: Q-5985-2016
MD, Professor, Chief Researcher of Immunogenetics Laboratory
Elena Polenok
Institute of Human Ecology Federal Research Center of Coal and Coal chemistry SB RAS
Email: egpolenok@mail.ru
ORCID iD: 0000-0002-9368-2340
SPIN-code: 3925-0185
Scopus Author ID: 6506567994
ResearcherId: Q-5381-2016
PhD (Candidate of Pharmacy), Leading Researcher of Immunochemistry Laboratory
Russian Federation, 10, Leningradsky Avenue, Kemerovo, 650065, RussiaLyudmila Gordeeva
Institute of Human Ecology, Federal Research Center of Coal and Coal chemistry SB RAS
Email: gorsib@rambler.ru
ORCID iD: 0000-0001-5870-7584
SPIN-code: 6662-4616
Scopus Author ID: 14052058500
ResearcherId: R-2781-2016
PhD (Candidate of Biology), Leading Researcher of Immunogenetics Laboratory
Russian Federation, 10, Leningradsky Avenue, Kemerovo, 650065, RussiaAlexander Antonov
Kuzbass Clinical Oncology Dispensary
Email: al0412@mail.ru
ORCID iD: 0000-0003-0802-9759
Chief of the Department of Breast Cancer
Russian Federation, 35, Volgogradskaya str., Kemerovo, 650036, RussiaPavel Bayramov
Kuzbass Clinical Oncology Dispensary
Email: bayramov_pavel82@mail.ru
ORCID iD: 0000-0002-4649-5892
Chief of Pathologoanatomical Department
Russian Federation, 35, Volgogradskaya str., Kemerovo, 650036, RussiaNatalia Verzhbitskaya
Kuzbass Clinical Oncology Dispensary
Email: verzhbitskaia@mail.ru
ORCID iD: 0000-0003-3860-825X
PhD (Candidate of Medicine), pathologist
35, Volgogradskaya str., Kemerovo, 650036, RussiaGleb Kolpinskiy
Kemerovo State Medical University; Kemerovo Clinical Diagnostic Сenter
Email: Glebss@mail.ru
ORCID iD: 0000-0002-5526-2687
SPIN-code: 6894-6419
Scopus Author ID: 56677706300
MD, Professor of Department of Radiology, Radiotherapy and Oncology; Main Physician
Russian Federation, 22A, Voroshilov str., Kemerovo, 650056, Russia; 53/1, Oktyabrsky Avenue, Kemerovo, 650066, RussiaReferences
- Glushkov A.N., Polenok E.G., Gordeeva L.A., Mun S.A., Kostyanko M.V., Kolpinckiy G.I., Vafin I.A., Antonov A.V., Verzhbitskaja N.E. Immune reactions to clinical carcinogens and steroid hormones in breast pre-cancer and cancer patients. Russian Journal of Immunology/Rossiyskiy immunologicheskiy Zhurnal, 2021, Vol. 24, no. 1, pp. 101-108. (In Russ.) [doi: 10.46235/1028-7221-977-IRT]
- Glushkov A.N., Polenok E.G., Gordeeva L.A., Mun S.A., Kostyanko M.V., Antonov A.V., Verzhbitskaya N.N., Bayramov P.V., Verzhbitskaya N.E., Kolpinskiy G.I. Cooperation of steroid hormones and hormone-specific autoantibodies in breast cancer progression. Fundamental and Clinical Medicine, 2023, Vol. 8, no. 2, pp. 19-32. (In Russ.). [doi: 10.23946/2500-0764-2023-8-2-19-32]
- Polenok E.G., Gordeeva L.A., Mun S.A., Kostyanko M.V., Antonov A.V., Verzhbitskaya N.E., Bairamov P.V., Kolpinskiy G.I.,Vafin I.A., Glushkov A.N. Cooperation of idiotypic and anti-idiotypic antibodies at the steroid-depended chemical carcinogenesis. Russian Journal of Immunology/Rossiyskiy immunologicheskiy Zhurnal, 2023, Vol. 25, no.1, pp. 35-48. (In Russ.) [doi: 10.46235/1028-7221-1177-CO]
- Chaudhri R.A., Schwartz N., Elbaradie K., Schwartz Z., Boyan B.D. Role of ERα 36 in membrane-associated signaling by estrogen. Steroids, 2014, Vol. 81, pp. 74-80. [doi: 10.1016/j.steroids.2013.10.020]
- Dressing G.E., Goldberg J.E., Charles N.J., Schwertfeger K.L., Lange C.A. Membrane progesterone receptor expression in mammalian tissues: a review of regulation and physiological implications. Steroids, 2011, Vol. 76, no. 1-2, pp. 11-17. [doi: 10.1016/j.steroids.2010.09.006]
- Greiner M., Pfeiffer D., Smith R.D. Principles and practical application of the receiver operating characteristic analysis for diagnostic test. Prev. Vet. Med., 2000, Vol. 45, pp. 23–41. [doi: 10.1016/S0167-5877(00)00115-X]
- Kampa M., Notas G., Pelekanou V., Troullinaki M., Andrianaki M., Azariadis K., Kampouri E., Lavrentaki K., Castanas E.. Early membrane initiated transcriptional effects of estrogens in breast cancer cells: First pharmacological evidence for a novel membrane estrogen receptor element (ERx). Steroids, 2012, Vol. 77, no. 10, pp. 959-967. [doi: 10.1016/j.steroids.2012.02.011]
- Li Q., Gao H., Yang H., Wei W., Jiang Y. Estradiol promotes the progression of ER+ breast cancer through methylation-mediated RSK4 inactivation. OncoTargets and Therapy, 2019, Vol. 12, pp. 5907-5916. [doi: 10.2147/OTT.S208988]
- Luconi M., Francavilla F., Porazzi I., Macerola B., Forti G., Baldi E. Human spermatozoa as a model for studying membrane receptors mediating rapid nongenomic effects of progesterone and estrogens. Steroids, 2004, Vol. 69, no. 8-9, pp. 553-559. [doi: 10.1016/j.steroids.2004.05.013]
- Maselli A., Capoccia S., Pugliese P., Raggi C., Cirulli F., Fabi A., Malorni W., Pierdominici M., Ortona E. Autoantibodies specific to estrogen receptor alpha act as estrogen agonists and their level correlate with breast cancer cell proliferation. Oncoimmunology, 2016, Vol. 5, no. 2, pp. e1074375. [doi: 10.1080/2162402X.2015.1074375]
- Mohammed H., Russell I.A., Stark R., Rueda O.M., Hickey T.E., Tarulli G.A., Serandour A.A., Birrell S.N., Bruna A., Saadi A., Menon S., Hadfield J., Pugh M., Raj G.V., Brown G.D., D'Santos C., Robinson J.L., Silva G., Launchbury R., Perou C.M., Stingl J., Caldas C., Tilley W.D., Carroll J.S. Progesterone receptor modulates ERα action in breast cancer. Nature, 2015, Vol. 523, no. 7560, pp. 313-317. [doi: 10.1038/nature14583]
- Norfleet A.M., Clarke C.H., Gametchu B., Watson C.S. Antibodies to the estrogen receptor- alpha modulate rapid prolactin release from rat pituitary tumor cells through plasma membrane estrogen receptors. FASEB J., 2000, Vol. 14, no. 1, pp. 157-165. [doi: 10.1096/fasebj.14.1.157]
- Sömjen D., Kohen F., Lieberherr M. Nongenomic effects of an anti- idiotypic antibody as an estrogen mimetic in female human and rat osteoblasts. J. Cell. Biochem., 1997, Vol. 65, no. 1, pp. 53-66. [doi: 10.1002/(SICI)1097-4644(199704)65:1<53::AID-JCB6>3.0.CO;2-Y]
Supplementary files
СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).