PATTERN OF MMP2 AND MMP9 EXPRESSION DEPENDS ON BREAST CANCER PATIENTS’ AGE
Keywords:breast cancer, matrix metalloproteinases, MMP-2, MMP-9
Background: Despite the large number of studies devoted to the study of the features of tumor microenvironment in breast cancer (BCa), presently there is no consensus on the features of MMP-2 and MMP-9 expression in the tumor tissue of BCa patients depending on the age. The aim of the study was to investigate the relationship between MMP-2 and -9 expression at the protein and mRNA levels in BCa tissues and the clinical and pathological features of BCapatientsin different age groups. Materials and Methods: The expression level of MMP-2 and -9in the BCa tissue of patients of two age groups (< 45 years and > 45 years) was studied using the bioinformatics method (UALCAN database), immunohistochemical method, and real-time PCR. Results: It was established that a characteristic feature of BCa in young patients is the low level of MMP2 mRNA against the background of increased expression of this gelatinase at the protein level, as well as decreased expression of MMP9 at both the mRNA and protein levels. When analyzing the correlation of the gelatinase expression indices in BCa tissue of young patients, depending on the clinical and pathological features, a significantly lower level of MMP-2 expression was recorded in BCa cases of stage II compared to the indices of stage I cases. High expression of MMP-2 and -9 was recorded in BCa tissue in node-positive cases and the basal molecular BCa subtype. Conclusions: The identified relationship between the expression of the studied gelatinases and such indices of BCa malignancy as its stage, positive regional lymph node status, and the molecular BCa subtype in young patients indicates the need for further research of the features of the tumor microenvironment to predict the cancer aggressiveness.
Di Mattei VE, Perego G, Taranto P, et al. Psychological issues in breast cancer survivors confronted with motherhood: Literature review and a call to action. Front Psychol 2023; 14: 1133204. doi:10.3389/fpsyg.2023.1133204
Azim HA, Partridge AH. Biology of breast cancer in young women. Breast Cancer Res 2014; 16: 427. doi:10.1186/s13058-014-0427-5
Mittal S, Brown NJ, Holen I.The breast tumor microenvironment: role in cancer development, progression and response to therapy. Expert Rev Mol Diagn 2018; 18: 227–243. doi:10.1080/14737159.2018.1439382
Lukianova NY, Borikun TV, Chekhun VF. Tumor microenvironment-derived miRNAs as prognostic markers of breast cancer. Exp Oncol 2019; 41:242–247. doi:10.32471/exp-oncology.2312-8852.vol-41-no-3.13615
Lyalkin S. Optimization of Chemotherapy of Patients with Metastatic Triple-negative Breast Cancer. Doctoral dissertation. National Cancer Institute: Kyiv, 2020. 366 p. (in Ukrainian).
Deepak KGK, Vempati R, Nagaraju GP, et al. Tumor microenvironment: challenges and opportunities in targeting metastasis of triple negative breast cancer. Pharmacol Res 2020; 153: 104683. doi:10.1016/j.phrs.2020.104683
Laronha H, Caldeira J. Structure and function of human matrix metalloproteinases. Cells 2020; 9: 1076. doi:10.3390/cells9051076
Li H, Qiu Z, Li F, Wang C. The relationship between MMP-2 and MMP-9 expression levels with breast cancer incidence and prognosis. Oncol Lett 2017; 14: 5865–5870. doi:10.3892/ol.2017.6924
Chekhun VF. Stroma as a regulator of tumor cell progression. Oncology 2009; 11: 164–165 (in Russian).
Ren F, Tang R, Zhang X, et al. Overexpression of MMP family members functions as prognostic biomarker for breast cancer patients: A systematic review and meta-analysis. PLoS One 2015; 10: e0135544. doi:10.1371/journal.pone.0135544
Somiari SB, Somiari RI, Heckman CM, et al. Circulating MMP2 and MMP9 in breast cancer – potential role in classification of patients into low risk, high risk, benign disease and breast cancer categories. Int J Cancer 2006; 119: 1403–1411. doi:10.1002/ijc.21989
Kim HJ, Park CI, Park BW, et al. Expression of MT-1 MMP, MMP2, MMP9 and TIMP2 mRNAs in ductal carcinoma in situ and invasive ductal carcinoma of the breast. Yonsei Med J 2006; 47: 333–342. doi:10.3349/ymj.2006.47.3.333
Thike AA, Chng MJ, Fook-Chong S, et al.Immunohistochemical expression of hormone receptors in invasive breast carcinoma: correlation of results of H-score with pathological parameters. Pathology 2001; 33: 21–25.
Zhang C, Li Y, Qian ZJ, et al. Dieckol from Ecklonia cava regulates invasion of human fibrosarcoma cells and modulates MMP-2 and MMP-9 expression via NF-κB pathway. Evid Based Complement Alternat Med 2011; 2011: 140462. doi:10.1155/2011/140462
Lukianova N, Zadvornyi T, Kashuba E, et al. Expression of markers of bone tissue remodeling in breast cancer and prostate cancer cells in vitro. Exp Oncol 2022; 44:39–46. doi:10.32471/exp-oncology.2312-8852.vol-44-no-1.17354
Têtu B, Brisson J, Wang CS, et al. The influence of MMP-14, TIMP-2 and MMP-2 expression on breast cancer prognosis. Breast Cancer Res 2006; 8: R28. doi:10.1186/bcr1503
Kuskunović-Vlahovljak S, Čamdžić N, Radović S, et al. Is the expression of matrix metalloproteinases (MMP-2, -9) and tissue inhibitors of metalloproteinases (TIMP-1, -2, and -3) associated with angiogenesis and clinicopathological features for breast cancer? J Health Sci 2017; 7:158–168. doi: 10.17532/jhsci.2017.460
Talvensaari-Mattila A, Pääkkö P, Turpeenniemi-Hujanen T. MMP-2 positivity and age less than 40 years increases the risk for recurrence in premenopausal patients with node-positive breast carcinoma. Breast Cancer Res Treat 1999; 58:287–293. doi:10.1023/a:1006326513176
Song N, Sung H, Choi JY, et al. Preoperative serum levels of matrix metalloproteinase-2 (MMP-2) and survival of breast cancer among Korean women. Cancer Epidemiol Biomarkers Prev 2012; 21:1371–1380. doi:10.1158/1055-9965.EPI-12-0293
How to Cite
Copyright (c) 2023 Experimental Oncology
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.