TUMOR-ASSOCIATED METALLOPROTEINASES IN SERUM OF PRIMARY BONE SARCOMA PATIENTS

N.E. Kushlinskii, I.V. Babkina, I.N. Kuznetsov, E.A. Korotkova, E.A. Ten, I.V. Bulycheva, Yu.N. Solovev, M.D. Aliev
N.N. Blokhin Russian Cancer Research Center of the RAMS, Russian Federation, 115478, Moscow, Kashirskoe shosse, 24

Introduction. Matrix metalloproteinase (MMP) – a family of extracellular zinc-containing proteases. There are currently 25 known MMP. Increased activity of MMP observed in some physiological processes – during the follicular phase of the menstrual cycle and during implantation of a fertilized oocyte. Known part of MMP in invasive tumor growth and metastasis. The aim of the study. Study of the content of metalloproteinases (MMP-2, MMP-7, MMP-9) and their inhibitor TIMP-1 in serum of patients with primary malignant tumors of bone and healthy age-matchedpersons to identify the possible correlation with the histological structure of the tumor. Methods. Examined 54 patients with bone tumors (29 males and 25 females) aged 14–59 years and 26 healthy subjects (14 men and 12 women) of the appropriate age. In all patients, diagnosis is confirmed by the data for the first time, and histology of the tumor. Typical osteosarcoma was diagnosed in 21 patients (39%), Ewing’s sarcoma – in 11 (20%), giant cell tumor of bone – in 9 (16%), primary chondrosarcoma – in 6 (11%), periosteal osteosarcoma – in 4 (8%), bone malignant fibrous histiocytoma – 3 (6%). Results. No significant differences in the content of MMP-2 and MMP-7 in the serum of healthy individuals and patients with bone tumors, as well as in the comparison of values with the histological structure of the tumor were found. The content MMP-9 in the serum of patients with malignant bone tumors was significantly lower than in healthy cases. TIMP-1 levels in a typical osteosarcoma and periosteal osteosarcoma especially when characterized by a very aggressive course were significantly higher than in healthy individuals, possibly because due to involvement of TIMP-1 in the mechanisms of tumor invasion and metastasis. Conclusions. A direct correlation between TIMP-1 and MMP-9 in the serum in typical osteosarcoma, periosteal osteosarcoma and Ewing’s sarcoma were found. The data suggest that the expression of TIMP-1 and MMP-9 may be linked to the pathogenic mechanisms associated with the growth of the typical and periosteal osteosarcoma and Ewing’s sarcoma, and may be the subject of further research.
Keywords: 
metalloproteinases, osteosarcoma, chondrosarcoma, Ewing’s sarcoma