| Autor: |
Kazanskaya GM; Institute of Molecular Biology and Biophysics, Timakova 2/12, Novosibirsk, 630117, Russia.; Meshalkin National Medical Research Center, Novosibirsk, Russia., Tsidulko AY; Institute of Molecular Biology and Biophysics, Timakova 2/12, Novosibirsk, 630117, Russia., Volkov AM; Meshalkin National Medical Research Center, Novosibirsk, Russia., Kiselev RS; Meshalkin National Medical Research Center, Novosibirsk, Russia.; Novosibirsk State Medical University, Novosibirsk, Russia., Suhovskih AV; Institute of Molecular Biology and Biophysics, Timakova 2/12, Novosibirsk, 630117, Russia.; Novosibirsk State University, Novosibirsk, Russia., Kobozev VV; Meshalkin National Medical Research Center, Novosibirsk, Russia., Gaytan AS; Novosibirsk State Medical University, Novosibirsk, Russia.; European Medical Centre, Moscow, Russia., Aidagulova SV; Novosibirsk State Medical University, Novosibirsk, Russia., Krivoshapkin AL; Novosibirsk State Medical University, Novosibirsk, Russia.; European Medical Centre, Moscow, Russia., Grigorieva EV; Institute of Molecular Biology and Biophysics, Timakova 2/12, Novosibirsk, 630117, Russia. elv_grig@yahoo.com.; Meshalkin National Medical Research Center, Novosibirsk, Russia. elv_grig@yahoo.com.; Novosibirsk State University, Novosibirsk, Russia. elv_grig@yahoo.com. |
| Abstrakt: |
Glycosaminoglycans are major components of brain extracellular matrix (ECM), although heparan sulfate (HS) contribution in brain physiology and carcinogenesis remains underinvestigated. This study examined HS content and distribution in glioblastoma multiforme (GBM) tissues in the context of potential molecular mechanisms underlying its deregulation in brain tumours. Totally, 42 tissue samples and paraffin-embedded tissues for 31 patients with different prognosis were investigated. HS expression was demonstrated in 50-55% of the GBM tumours by immunohistochemistry (IHC), while almost no HS content was detected in the surrounding paratumourous brain tissues. Heterogeneous HS distribution in the HS-positive tumours was more related to the necrosis or glandular-like brain zones rather than glioma cells with high or low Ki-67 index. According the Kaplan-Meier curves, HS accumulation in glioma cells was associated with low relapse-free survival (RS) of the GBM patients (p < 0.05) and was likely to be due to the increased transcriptional activity of HSPG core proteins (syndecan-1, 2-3 fold; glypican-1, 2,5 fold; perlecan/HSPG2, 13-14 fold). Activation of perlecan/HSPG2 expression correlated with the patients' survival according Kaplan-Meier (p = 0.0243) and Cox proportional-hazards regression (HR = 3.1; P(Y) = 0.03) analyses, while up-regulation of syndecan-1 and glypican-1 was not associated with the patients survival. Taken together, the results indicate that increase of HS content and up-regulation of perlecan/HSPG2 expression in glioblastoma tissues contribute to tumour development through the transformation of brain extracellular matrix into tumour microenvironment, and represent negative prognostic factors for glioblastoma progression. |
