350 rub
Journal №8 for 2014 г.
Article in number:
Vegf signaling pathway components and matrix metalloproteinases - in tumors of patients with ovarian neoplasms
Keywords: VEGF VEGFR-1 VEGFR-2 matrix metalloproteinase 2 matrix metalloproteinase 7 matrix metalloproteinase 9 ovarian tumors
Authors:
D.N. Kushlinsky - Physician cancers, Research Center for Obstetrics, Gynecology and Perinatology, Moscow, Russia
E.S. Gershtein - Dr.Sc. (Biol.), Professor, Russian Cancer Research Center of N.N. Blokhin Russian Academy of Medical Sciences, Moscow, Russia. E-mail: esgershtein@gmail.com
I.V. Tereshkina - Ph.D. (Med.), Moscow State University of Medicine and Dentistry named A.I. Evdokimov
V.D. Ermilova - Ph.D. (Med.), Russian Cancer Research Center of N.N. Blokhin Russian Academy of Medical Sciences, Moscow, Russia
K.P. Laktionov - Dr.Sc. (Med.), Professor, Russian Cancer Research Center of N.N. Blokhin Russian Academy of Medical Sciences, Moscow, Russia
L.V. Adamyan - Dr.Sc. (Med.), Professor, Academician RAS, Research Center for Obstetrics, Gynecology and Perinatology, Moscow, Russia
Abstract:
Neoangiogenesis is one of the key factors necessary for tumor growth and spread. The central place in the regulation of this process belongs to vascular endothelial growth factor (VEGF) that affects tumor progression in complex cooperation with matrix metalloproteases(MMP). All these proteins are regarded as potential diagnostic and prognostic markers and objects of molecular targeted therapy. Aim of the study - сomparative evaluation of tumor VEGF, its type 1 and type 2 receptors, and some representatives of matrix metalloproteinase family (MMP-2, 7 and 9) content in ovarian cancer, borderline and benign tumors, and analysis of the associations of these markers with ovarian cancer clinico-pathologic features. Concentrations of the markers studied were measured in tumor cytosols of 50 ovarian cancer, 9 borderline and 22 benign ovarian tumor patients by standard direct ELISA kits (Quantikine, R&D, USA). VEGF level was significantly increased and matrix metalloproteinase (MMP) 2 level was decreased in ovarian cancer tissue as compared to benign tumors. A trend towards MMP-7 and MMP-9 elevation, and VEGFR2 decrease in cancer tissue was also observed. Highly significant negative association was found between VEGF and MMP-2 levels, while positive correlations were revealed between VEGF and MMP-7, VEGF and MMP-9, MMP-2 and VEGFR2. In the tumors examined after presurgical therapy а comparative normalization of parameters studied was observed: VEGF level significantly decreased, and MMP-2 and VEGFR2 levels increased. Significant differences in marker levels were found in relation to ovarian cancer histological type, and an increase of VEGFR2 level in stage III as compared to stage I and that of MMP-7 in stage III as compared to stage II tumors was demonstrated. Multidirectional changes of VEGF-signaling system components and some MMPs were demonstrated in ovarian cancer as compared to benign tumor tissue. High VEGF level in ovarian cancer tissue confirms the prospects of including antiangiogenic drugs in ovarian cancer therapeutic regimens.
Pages: 47-52
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