22P - Glial cells as a marker of stem cell-based glioblastoma multiforme treatment effectiveness

Date 05 November 2016
Event ESMO Symposium on Immuno-Oncology 2016
Session Lunch and general poster viewing
Presenter Sergey Zaitsev
Citation Annals of Oncology (2016) 27 (suppl_8): viii4-viii17. 10.1093/annonc/mdw527
Authors S. Zaitsev1, I.S. Bryukhovetskiy2, P.V. Mischenko3, E.V. Milkina2, Y.S. Khotimchenko4
  • 1School Of Biomedicine, Far Eastern Federal University, 690000 - Vladivostok/RU
  • 2School Of Biomedicine, Far Eastern Federal University, Vladivostok/RU
  • 3Far Eastern Federal University, Zhirmunskiy Institute of Marine Biology, Vladivostok/RU
  • 4Far Eastern Federal University, Zhirmunsky Institute of Marine Biology, Vladivostok/RU

Abstract

Aim/Background

Glioblastoma multiforme (GBM) is an absolutely fatal disease with patients rarely reaching their second year. Invasive growth and presence of cancer stem cells (CSC), key characteristics of GBM, are major factors that render standard treatment protocols ineffective. Development of treatment methods based on stem cells (SC) should circumvent the shortcomings of existing approaches, but the lack of objective effectiveness evaluation criteria limits their clinical use. The present study is aimed at evaluating glia as a possible SC-based therapy effectiveness marker.

Methods

Cell lines: rat glioma C6; human CD34+ rich mononuclears (HSC). Glioblastoma model: stereotaxic intracranial implantation of C6 into Wistar rats. Immunofluorescence: p53, nestin, GFAP, βIII-tubulin, S100, CXCR4, DAPI. Histology: Coronal hematoxylin-eosin stained slices. Immunohistochemistry: PCNA, TGF-β2, IBA-1, CXCR4, IL1β.

Results

Massive tumors identified by 10th day following C6 implantation consisted of polymorphic, polymorphonuclear cells and light, diffuse glia infiltration. By the 20th day neoplastic tissue was heavily vascularized, glia began concentrating along tumor border (mirroring mesenchyme infiltration by GBM) and near blood vessels. Signs of cell death began emerging, reaching a peak by 30th day. Tumors consisted of large necrotic areas and thick nodule-like clusters around the blood vessel, rich in SC-like cells. Glial cells were found along tumor border and within blood vessel endothelium. TGF-β2 and IL1β expression corresponded to glia localization. Mean animal survival was 34.0±8.1 days. Intravenous injection of HSC didn’t influence glia distribution dynamics, whilst it was mirrored by increased amount of SC-like cells concentration. However, pro-oncogenic cytokine expression was decreased. Survival reached 39,5±8,8 days.

Conclusions

GBM CSC attracts glia and SC which stimulates tumor progression by secreting epithelial-mesenchymal transition (EMT) inducing cytokines. EMT enchants CSC resistance and increases its hypoxia-driven motility. Resulting migration determines GBM development. Introduction of HSC interferes with EMT induction thus slowing GBM progression. This highlights prospects of using SC for GBM treatment development.

Clinical trial identification

Legal entity responsible for the study

Far Eastern Federal University

Funding

The research was sponsored by Russian Science Foundation (Project 14-15-00084)

Disclosure

All authors have declared no conflicts of interest.