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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

1526 - Study of the activation of TLR receptors in neurospheres from glioblastoma cells in vitro

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

David Albert Bellver

Citation

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

Authors

D. Albert Bellver1, R. Gil-Benso1, A. Martínez2, T. San-Miguel1, L. Muñoz-Hidalgo1, A. Carratalá1, D. Gozalbo2, C. López-Ginés1, M. Cerdá-Nicolás1, M.L. Gil2, J. Megías1

Author affiliations

  • 1 Pathology, University of Valencia, 46010 - Valencia/ES
  • 2 Microbiology And Ecology, University of Valencia, 46100 - Burjassot/ES
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Resources

Abstract 1526

Background

Glioblastoma (GB) is the most aggressive brain tumor known. GB stem cells (GSC) are resistant to ordinary therapy and contribute to the development of recurrences. Toll-like receptors (TLR) are expressed in immunity cells to recognize multiple ligands from multiple infectious agents to unleash the immune response. TLRs are also expressed in neural cells, such as GB and neural stem cells, where its activation may imply cell differentiation. The aim of this study was to prove whether the stimulation of GSC TLRs induces a phenotype more sensitive to therapy and less aggressive.

Methods

Two GB cell lines were used: U-87 and U-118 (ATCC), cultured in the presence of Neurobasal® medium and in the absence of fetal bovine serum. The culture obtained was formed by neurospheres, which include a high proportion of GSC. On the one hand, the enrichment in GSC was confirmed by flow cytometry by the expression of stem cell markers CD133 and CD44. On the other hand, the analysis of TLR expression was performed by RT-PCR. According to its TLR expression, neurosphere cells were exposed to the pertinent TLR ligands for 24 hours in vitro and cultured in the presence or absence of temozolomide (TMZ). After stimulation, the expression of CD133 and CD44 was measured by flow cytometry.

Results

Flow cytometry results showed a higher proportion of GSC in the culture with Neurobasal®. RT-PCR results demonstrated expression in stem cells of the genes corresponding to TLR2, TLR3, TLR4 and TLR6 receptors. Flow cytometry post-stimulation proved a decrease of stem cell markers in the ligands of the TLR2 and TLR4 in both lines. Cultures with TMZ did not show significantly altered expression of GSC, although survival was lower than cultures without TMZ.

Conclusions

These results show a relation between the activation of the TLR and the increase of the differentiation rate in GSCs, especially through TLR2 and TLR4. Based on the results obtained, a new therapy for GB treatment, might be possible, which would include the differentiation of GSC by the exposition to TLR2 and TLR4 ligands, previous or concomitant to chemotherapy.

Clinical trial identification

Legal entity responsible for the study

University of Valencia.

Funding

Has not received any funding.

Editorial Acknowledgement

Disclosure

All authors have declared no conflicts of interest.

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