Metalloproteineses 1, 2 and their tissue inhibitors serum level in bone tumor patients

Background. Numerous studies have proved the participation of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) in the pathogenesis of diseases of various etiologies, including in tumor transformation, as well as in the processes of invasion and metastasis. The involvement of TIMP-1 and TIMP-2 in the processes of growth and progression of osteosarcoma was demonstrated in the U-2OS, MG-63 and OS-732 cell lines. There are small amount of clinical studies for bones tumors, but they show differences in expression of MMP and TIMP in the tumor and surrounding tissues, both in borderline and malignant bones tumors. Aim of the study. The study of the content of tissue inhibitors of MMPs TIMP-1 and TIMP-2 type in the most accessible biological material - the blood serum of patients with primary malignant and borderline neoplasm of bones and apparently healthy people of the corresponding age to identify a possible relationship with the morphological tumor’s structure and the prognosis of the disease. Materials and methods. 128 patients with bone tumors (69 men and 59 women) and 42 apparently healthy donors of the corresponding age were examined. The diagnosis of all patients, t was established for the first time and confirmed by histological examination of the tumor. Malignant bones tumors were diagnosed in 108 (84%), borderline bones tumors - in 20 (16%) patients. The studies were performed by an enzyme immunoassay TIMP-1, TIMP-2 in the blood serum of patients before the start of a specific treatment with the help of ready-made reagent kits of the firm «R&D» (USA). Results. In patients with malignant and borderline bone tumors, significantly higher concentrations of TIMP-1 and TIMP-2 were found in the blood serum than in the control, independent of the stage of the disease, histological structure, degree of differentiation and tumor localization in bones of various structures. According to the multivariate analysis, the threshold levels of TIMP-1 greater than 343 ng/ml and TIMP-2 greater than 120 ng/ml can be considered as significant and independent factors predicting the overall survival of patients with bone sarcomas. Conclusion. The obtained results testify to the prospects of further study of TIMP-1 and TIMP-2 in peripheral blood at bones neoplasm for study the possibility of using them as markers of disease prognosis.

TIMP-1, TIMP-2, bones tumors, overall survival, prognosis

1. Рогова ЛН, Шестернина НВ, Замечник ТВ, Фастова ИА. Матриксные металлопротеиназы, их роль в физиологических и патологических процессах. Вестник новых медицинских технологий. 2011;18(2):86-89.

2. Маркелова ЕВ, Здор ВВ, Романчук АЛ, Бирко ОН. Матриксные металлопротеиназы: их взаимосвязь с системой цитокинов, диагностический и прогностический потенциал. Иммунология, аллергология, инфектология. 2016;2:11-22.

3. Герштейн ЕС, Кушлинский НЕ. Клинические перспективы исследования ассоциированных с опухолью протеаз и их тканевых ингибиторов у онкологических больных. Вестник Российской академии медицинских наук. 2013;5:16-27.

4. Герштейн ЕС, Кушлинский ДН, Адамян ЛВ, Терешкина ИВ, Лактионов КП. Матриксные металлопротеиназы и их тканевые ингибиторы в клиническом течении и прогнозе рака яичников. Мол Мед. 2013;6:11-20.

5. Герштейн ЕС, Кушлинский НЕ. Матриксные металлопротеиназы и компоненты системы активации плазминогена в патогенезе и клиническом течении рака толстой кишки. Патогенез. 2013;11(3):4-12.

6. Wang Z, Li Y, Zhou F et al. ß-elemene enhances anticancer bone neoplasms efficacy of paclitaxel through regulation of GPR124 in bone neoplasms cells. Oncol Lett. 2018;16(2):2143-2150.

7. Wang Y, Kong D. LncRNA GAS5 Represses Osteosarcoma Cells Growth and Metastasis via Sponging MiR-203a. Cell Physiol Biochem. 2018;45(2):844-855.

8. Liu Z, Ren Y, Zhu F. Expression of MMP-2 and TIMP-3 with incidence and prognosis of giant-cell tumor of the bone. Oncol Lett. 2018;16(1):721-726.

9. Tsai CH, Yang DY, Lin CY et al. Sphingosine-1-phosphate suppresses chondrosarcoma metastasis by upregulation of tissue inhibitor of metalloproteinase 3 through suppressing miR-101 expression. Mol Oncol. 2017;11(10):1380-1398.

10. Yao M, Wang X, Zhao Y et al. Expression of MMPs is dependent on the activity of mitogen-activated protein kinase in chondrosarcoma. Mol Med Rep. 2017;15(2):915-921.

11. Кушлинский НЕ, Соловьев ЮН, Бабкина ИВ, Герштейн ЕС, Булычева ИВ. Матриксные металлопротеиназы 2, 7, 9 и тканевой ингибитор матриксных металлопротеиназ 1-го типа в сыворотке крови больных опухолями костей. Бюлл Эксп Биол Мед. 2010;149(2):194-196