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Chemoradiotherapy increases intratumor heterogeneity of HPSE expression in the relapsed glioblastoma tumors. / Suhovskih, Anastasia V.; Kazanskaya, Galina M.; Volkov, Alexander M. et al.
In: International Journal of Molecular Sciences, Vol. 21, No. 4, 1301, 14.02.2020.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Chemoradiotherapy increases intratumor heterogeneity of HPSE expression in the relapsed glioblastoma tumors
AU - Suhovskih, Anastasia V.
AU - Kazanskaya, Galina M.
AU - Volkov, Alexander M.
AU - Tsidulko, Alexandra Y.
AU - Aidagulova, Svetlana V.
AU - Grigorieva, Elvira V.
N1 - Publisher Copyright: © 2020 by the authors. Licensee MDPI, Basel, Switzerland. Copyright: Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/2/14
Y1 - 2020/2/14
N2 - Adjuvant chemoradiotherapy is a standard treatment option for glioblastoma multiforme (GBM). Despite intensive care, recurrent tumors developed during the first year are fatal for the patients. Possibly contributing to this effect, among other causes, is that therapy induces changes of polysaccharide heparan sulfate (HS) chains in the cancer cells and/or tumor microenvironment. The aim of this study was to perform a comparative analysis of heparanase (HPSE) expression and HS content in different normal and GBM brain tissues. Immunohistochemical analysis revealed a significant decrease of HPSE protein content in the tumor (12-15-fold) and paratumorous (2.5-3-fold) GBM tissues compared with normal brain tissue, both in cellular and extracellular compartments. The relapsed GBM tumors demonstrated significantly higher intertumor and/or intratumor heterogeneity of HPSE and HS content and distribution compared with the matched primary ones (from the same patient) (n = 8), although overall expression levels did not show significant differences, suggesting local deterioration of HPSE expression with reference to the control system or by the treatment. Double immunofluorescence staining of various glioblastoma cell lines (U87, U343, LN18, LN71, T406) demonstrated a complex pattern of HPSE expression and HS content with a tendency towards a negative association of these parameters. Taken together, the results demonstrate the increase of intratumor heterogeneity of HPSE protein in relapsed GBM tumors and suggest misbalance of HPSE expression regulation by the adjuvant anti-GBM chemoradiotherapy.
AB - Adjuvant chemoradiotherapy is a standard treatment option for glioblastoma multiforme (GBM). Despite intensive care, recurrent tumors developed during the first year are fatal for the patients. Possibly contributing to this effect, among other causes, is that therapy induces changes of polysaccharide heparan sulfate (HS) chains in the cancer cells and/or tumor microenvironment. The aim of this study was to perform a comparative analysis of heparanase (HPSE) expression and HS content in different normal and GBM brain tissues. Immunohistochemical analysis revealed a significant decrease of HPSE protein content in the tumor (12-15-fold) and paratumorous (2.5-3-fold) GBM tissues compared with normal brain tissue, both in cellular and extracellular compartments. The relapsed GBM tumors demonstrated significantly higher intertumor and/or intratumor heterogeneity of HPSE and HS content and distribution compared with the matched primary ones (from the same patient) (n = 8), although overall expression levels did not show significant differences, suggesting local deterioration of HPSE expression with reference to the control system or by the treatment. Double immunofluorescence staining of various glioblastoma cell lines (U87, U343, LN18, LN71, T406) demonstrated a complex pattern of HPSE expression and HS content with a tendency towards a negative association of these parameters. Taken together, the results demonstrate the increase of intratumor heterogeneity of HPSE protein in relapsed GBM tumors and suggest misbalance of HPSE expression regulation by the adjuvant anti-GBM chemoradiotherapy.
KW - Adjuvant chemoradiotherapy
KW - Disease relapse
KW - Glioblastoma multiforme
KW - Heparan sulfate
KW - Heparanase expression
KW - Intratumor heterogeneity
KW - SURVIVAL
KW - glioblastoma multiforme
KW - intratumor heterogeneity
KW - GLYCOSAMINOGLYCANS
KW - GLIOMA
KW - heparan sulfate
KW - HEPARANASE EXPRESSION
KW - CLONING
KW - GROWTH
KW - SPALAX
KW - TARGETS
KW - adjuvant chemoradiotherapy
KW - heparanase expression
KW - UP-REGULATION
KW - disease relapse
UR - http://www.scopus.com/inward/record.url?scp=85079513783&partnerID=8YFLogxK
U2 - 10.3390/ijms21041301
DO - 10.3390/ijms21041301
M3 - Article
C2 - 32075104
AN - SCOPUS:85079513783
VL - 21
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 4
M1 - 1301
ER -
ID: 23523239