Chemoradiotherapy Increases Intratumor Heterogeneity of HPSE Expression in the Relapsed Glioblastoma Tumors.
Anastasia V SuhovskihGalina M KazanskayaAlexander M VolkovAlexandra Y TsidulkoSvetlana V AidagulovaElvira V GrigorievaPublished in: International journal of molecular sciences (2020)
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.
Keyphrases
- poor prognosis
- binding protein
- acute lymphoblastic leukemia
- acute myeloid leukemia
- diffuse large b cell lymphoma
- end stage renal disease
- single cell
- early stage
- gene expression
- rectal cancer
- stem cells
- long non coding rna
- chronic kidney disease
- white matter
- multiple myeloma
- hodgkin lymphoma
- multiple sclerosis
- small molecule
- radiation therapy
- peritoneal dialysis
- prognostic factors
- combination therapy
- patient reported outcomes