Oops, you're using an old version of your browser so some of the features on this page may not be displaying properly.

MINIMAL Requirements: Google Chrome 24+Mozilla Firefox 20+Internet Explorer 11Opera 15–18Apple Safari 7SeaMonkey 2.15-2.23

Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

4110 - Extracellular matrix of normal brain tissue is affected by temozolomide during anti-glioblastoma treatment

Date

21 Oct 2018

Session

Poster display session: Basic science, Endocrine tumours, Gastrointestinal tumours - colorectal & non-colorectal, Head and neck cancer (excluding thyroid), Melanoma and other skin tumours, Neuroendocrine tumours, Thyroid cancer, Tumour biology & pathology

Presenters

Alexandra Tsidulko

Citation

Annals of Oncology (2018) 29 (suppl_8): viii1-viii13. 10.1093/annonc/mdy268

Authors

A. Tsidulko1, C. Bezier2, G. de La Bourdonnaye3, A.V. Suhovskih1, G. Kazanskaya4, S. Aidagulova5, E.V. Grigorieva1

Author affiliations

  • 1 Laboratory Of Glycobiology, Federal Research Center of Fundamental and Translational Medicine, 630117 - Novosibirsk/RU
  • 2 Molecular And Cellular Biology, Pierre et Marie Curie University, 75 005 - Paris/FR
  • 3 Biochemical Engineering, National Institute for Applied Sciences, 31400 - Toulouse/FR
  • 4 Dept. Of Pathomorphology, Meshalkin National Medical Research Center, Novosibirsk/RU
  • 5 Dept. Of Histology, Embryology And Cytology, Novosibirsk State Medical University, Novosibirsk/RU
More

Resources

Abstract 4110

Background

Temozolomide (TMZ) is a main drug for chemotherapy of glioblastoma multiforme (GBM). During the treatment, both GBM tumour and surrounding normal brain are exposed to the drug, and its effects on the normal brain tissue are not investigated. Survival and invasion of GBM cells depend not only on their characteristics but also on the structure of extracellular matrix (ECM) of brain tissue, which consists mainly of glycosylated molecules such as proteoglycans (PGs) and glycosaminoglycans (GAGs). Here, we aimed to investigate the effects of TMZ on PGs and GAGs expression in normal brain tissue.

Methods

Two-month-old Wistar rats were used in the study, and effects of TMZ treatment on PGs (syndecan-1, glypican-1, perlecan, decorin, biglycan, lumican, brevican, neurocan, CSPG4/NG2, aggrecan) were studied using real-time RT-PCR and IHC analyses.

Results

Treatment with TMZ had almost no effects on the overall transcriptional activity of the PGs core proteins in normal brain tissue but resulted in a 2-fold increase of GAGs content (both heparin sulfates and chondroitin sulfates). Different TMZ-based drugs demonstrated different effects on the PGs core proteins expression - treatment with some of them resulted in significant decrease in syndecan-1, glypican-1, perlecan and lumican expression. Moreover, treatment with combination of TMZ and dexamethasone, commonly used to treat glioma-induced edema, led to the most dramatic changes in PGs composition in the brain tissue at both core protein and GAG levels.

Conclusions

The obtained results demonstrate that chemotherapy with temozolomide affects proteoglycan composition and ECM structure in normal brain tissue. These changes might be involved in the formation of the tumourigenic niche for the expansion of the residual glioma cells and the disease progression.

Clinical trial identification

Legal entity responsible for the study

Federal Research Center of Fundamental and Translational Medicine.

Funding

Russian Science Foundation (RSF grant 16-15-10243). Tsidulko A. was funded by individual scholarship of Russian Federation President for young scientists (SP-5435.2018.4).

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings