Immunohistochemical study of MMP-2, TIMP-1 in hyperplastic polyps and intestinal-type gastric adenocarcinoma.
DOI:
https://doi.org/10.26641/1997-9665.2017.3.21-28Keywords:
stomach neoplasms, polyps, adenocarcinoma, matrix metalloproteinases, tissue inhibitor of metalloproteinase-1.Abstract
Background. The process of extracellular matrix degradation, provided by the matrix metalloproteinases system, plays an important role in cancerogenesis. Objective. To study the features of immunohistochemical expression of MMP-2, TIMP-1 by hyperplastic polyps’ cells and intestinal-type gastric adenocarcinoma cells. Methods. Pathohistological and immunohistochemical studies of hyperplastic polyps from 30 patients (age ranged from 52 to 73 years), intestinal-type gastric adenocarcinoma from 30 patients (age ranged from 49 to 86 years) were investigated. Results. It has been established that hyperplastic polyps’ epitheliocytes and stromal cells are characterized by the low MMP-2 and TIMP-1 expression levels, intestinal-type gastric adenocarcinoma cancer cells – by the low expression levels of these markers, while the cells of the carcinoma microenvironment are characterized by the medium expression levels of the examined markers. The cells of the microenvironment of the non-invasive carcinoma are characterized by the higher TIMP-1 expression level, compared to the cells of microenvironment of the invasive cancer. The direct correlations between the MMP-2 and TIMP-1 expression levels in the cancer cells and the cells of cancer microenvironment, and also the reverse correlation between the TIMP-1 and caspase-3 expression levels in the cancer cells were revealed. Conclusion. This data evidence the leading role of the cancer microenvironment cells in the process of extracellular matrix degradation, and also the close association between the stromolitic activity of the various cellular components of the carcinoma. Moreover, the anti-apoptotic effect of TIMP-1 in intestinal-type gastric adenocarcinoma was revealed.
References
- Korotkova EA, Ivannikov AA, Ognerubov NA, Gershteyn ES, Chang VL. [Gastric cancer: mo-lecular-genetic features]. Vestnik TGU. 2014;19(3):357-69. Russian.
- Zenyukov AS, Borovskaya TF, Stilidi IS, Nikulin MP, Kurpas EK, Zenyukova TV, Bekov SV, Sagaidak SB. [Expression of matrix metalloproteinases-2 and -9 in gastric cancer: clini-cal and morphological features]. Vestnik RONTs im. N N Blohina RAMN. (2010);21(4):23–30. Russian.
- Markelova EV, Zdor VV, Romanchuk AL, Birko ON. [Matrix metalloproteinases: relationship with cytokine system, diagnostic and prognostic potential]. Immunopatologiya, allergologiya, infektologiya. (2016);2:11-22. Russian.
- Poteryaeva ON. [Matrix metalloproteinases: structure, regulation, role in development of patho-logical conditions]. Meditsina i obrazovanie v Sibiri. (2010);5:52-8. Russian.
- Sampieri CL, de la Peña S, Ochoa-Lara M, Zenteno-Cuevas R, León-Córdoba K. Expression of matrix metalloproteinases 2 and 9 in human gastric cancer and superficial gastritis. World Journal of Gastroenterology. (2010);16(12):1500–5.
- Mroczko B, Lukaszewicz-Zaj`c M, Groblewska M, Czyzewska Z, Gryko M, Guziñska-Ustymowicz K, Kemona A, Kêdra B, Szmitkowski M. Expression of tissue inhibitors of metalloprotein-ase 1 (TIMP-1) in gastric cancer tissue. Folia Histochemica et Cytobiologia. 2009;47(3):511–6.
- Song G, Xu S, Zhang X, Wang Y, Xiao Ch, Jiang T, Wu L, Zhang T, Sun X, Zhong L, Zhou Ch, Wang Zh, Peng Zh, Chen J, Wang X. TIMP1 is a prognostic marker for the progression and metastasis of colon cancer through FAK-PI3K/AKT and MAPK pathway. Journal of Experimental & Clinical Cancer Research. 2016;35:148–54.
- Nalluri S, Gupta S, Kutiyanawalla A, Gayatri S, Lee BR, Jiwani S, Rojiani AM, Rojiani MV. TIMP-1 Inhibits Apoptosis in Lung Adenocarcino-ma Cells via Interaction with Bcl-2. PLOS one. (2015); 9: 256–264.
- Burlaka AP, Ganusevich II, Gafurov MR, Lukin SM, Sidorik EP. Stomach Cancer: Intercon-nection between the Redox State, Activity of MMP-2, MMP-9 and Stage of Tumor Growth. Cancer Microenviroment. (2016);9:27–32.
- Bornschein J, Seidel T, Langner C, Link A, Wex T, Selgrad M, Jechorek D, Meyer F, Bird-Lieberman E, Vieth M, Malfertheiner P. MMP2 and MMP7 at the invasive front of gastric cancer are not associated with mTOR expression. Diagnostic Pa-thology. 2015;10:212–7.
- Zhang DY, Wang Y, Zhang GQ, Chu XQ, Zhou Y. Correlations of MMP-2 and TIMP-2 gene polymorphisms with the risk and prognosis of gastric cancer. International Journal of Clinical and Ex-perimental Medicine. 2015;8(11):20391–401.
- Chen Y, Wei X, Guo C, Jin H, Han Zh, Qiao T, Wu K, Fan D. Runx3 suppresses gastric cancer metastasis through inactivation of MMP9 by upregulation of TIMP-1. International Journal of Cancer. 2011;129:1586–98.
- Hwang TL, Changchien TT, Wang CC, Wu CM. Claudin 4 expression in gastric cancer cells enhances the invasion and is associated with the increased level of matrix metalloproteinase 2 and 9 expression. Oncology Letters. 2014;8:1367–71.
- Tumanskyi VO, Yevsieiev AV, Kovalenko IS, Zubko MD, inventors; Zaporozhye State Medical University, assignee. Method of photo digital morphometrical study of immunohistochemical micropreparations. Ukraine patent UA 99314. 2015. Int. CI. G01N 21/00, G06K 9/0. Ukrainian.
- Tumanskiy VA, Khrystenko TA. Compara-tive immunohistochemical characteristic of expres-sion levels of Ki-67, p53, caspase-3 in non-invasive and invasive intestinal-type gastric adenocarcinoma. Pathologia. 2016;2:70-5. DOI: 10.14739/2310-1237.2016.2.81333.
- Sulzmaier FJ, Jean C, Schlaepfer DD. FAK in cancer: mechanistic findings and clinical applica-tions. Nat Rev Cancer. 2014 Sep;14(9):598-610. doi: 10.1038/nrc3792.
Downloads
How to Cite
Issue
Section
License
Copyright (c) 2018 Morphologia

This work is licensed under a Creative Commons Attribution 4.0 International License.
The authors reserve the right to authorship of their work and transfer to the Journal the right to the first publication of this work under the terms of a license Creative commons Attribution 4.0 International (CC BY 4.0), which allows other people to freely distribute the published work with a mandatory reference to the authors of the original work and the first publication of the work in this journal.By submitting a manuscript to the editorial office of the Journal ‘Morphologia’ authors agree to transfer the rights to protect and use the manuscript (all supplemental materials, particularly protected objects such as photos, drawings, diagrams, tables, etc.), including the reproduction in the press and distribution via the Internet; translation of the manuscript into any language; export and import of journal copies with the Authors’ article in order to make it available for public. Authors convey the rights mentioned above to the editorial office without any temporal or territorial limitation all over the world.
The Authors guarantee that they have the exclusive rights to use the material transferred to editorial office. Editors are not responsible to third parties for contraventions of warranty given by the Authors. The considered rights are transferred to the editorial office since the moment when the current issue is signed for publishing. Reproduction of materials published in the Journal by other individuals and legal entities is possible only with the consent of Editorial office, with the obligatory indication of the full bibliographic reference of the primary publication. The Authors reserve the right to use the published material, its fragments and parts for teaching materials, oral presentations, dissertation thesis prepararion with obligatory bibliographic citation of the original paper. Electron copy of the published article, downloaded from official journal web-site in .pdf format may be put by authors on the official web-site of their institutions, any other official resources with open access.
