RANK/RANKL/OPG SYSTEM COMPONENTS AND INTERLEUKINS 6, 8 16 IN BLOOD SERUM OF PATIENTS WITH PRIMARY BONE NEOPLASMS

DOI: https://doi.org/None

N.E. Kushlinskii (1), E.S. Gershtein (1), Yu.S. Timofeev (1), E.A. Korotkova (1), I.V. Babkina (3), A.A. Zuev (1), A.V. Bondarev (2), M.Yu. Schupak (2), Yu.N. Soloviev (1), M.D. Aliev (1) 1 -N.N. Blokhin Russian Cancer Research Center, Kashirskoye shosse, 24, Moscow, 115478, Russian Federation; 2 -Мoscow oncological clinic №62, Greenwich Istra, 27, p/о Stepanovsroye, Krasnogorsky district, , Мoscow region, 143423, Russian Federation; 3 -Moscow State University of Medicine and Dentistry т amed after A.I. Evdokimov, Delegatskaya Str., 20, Moscow, Russian Federation, 127473

Introduction. RANK/RANKL/OPG ligand-receptor system is a key player in bone tissue homeostasis directly regulating osteoclast differentiation and osteolysis. Many pathologic processes imposed by impairments in bone remodeling including tumor growth and metastasizing are associated with misbalance of this system. Aim of the study. Comparative evaluation of RANK/RANKL/OPG and some proinflammatory cytokines (IL6, 8, 16) levels in blood serum of primary bone neoplasms’ patients and practically healthy persons, and analysis of associations between these markers and principal clinico-pathologic characteristics of bone tumors. Material and methods. 101 patient with malignant bone tumor (37 – osteosarcoma, 41 – chondrosarcoma, 12 – chordoma, 7 – Ewing sarcoma, 2 – pleomorhic undifferentiated sarcoma, 2 – fibrosarcoma), 32 patients with borderline giant cell bone tumor (GCBT), and 30 benign bone tumor patients were involved. Control group comprised 71 persons. OPG, sRANKL, sRANK, IL-6, 8, 16 serum levels were measured by standard ELISA kits. Results. Measurable RANK levels were detected in blood serum of less than 50% of malignant and benign bone tumor patients and control persons; the median of RANK concentration in GCBT patients comprised 57 pg/ml. Serum sRANKL and OPG levels in GCBT patients’ were increased both in relation to control, and to malignant bone tumor patients. OPG level was also markedly increased in patients with malignant and benign neoplasms as compared to control, while IL-6 was significantly increased in benign and borderline tumor patients as compared to control and patients with benign lesions. The degree and direction of changes in RANK/sRANKL/OPG system depended also on histological type of malignant bone tumors. Conclusion. The changes revealed in this study testify to the disturbances in the balance of activators and inhibitors of osteolysis in patients with primary bone tumors in depending on the character of neoplasm (malignant, borderline or benign) and histological structure of malignant tumors.
Keywords: 
bone tumors, RANK, RANKL, OPG, IL-6, IL-8, IL-16, blood serum
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