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Review
. 2017 Aug 21;8(49):86947-86968.
doi: 10.18632/oncotarget.20372. eCollection 2017 Oct 17.

Interest of integrins targeting in glioblastoma according to tumor heterogeneity and cancer stem cell paradigm: an update

Laure Malric  1 , Sylvie Monferran  1   2 , Julia Gilhodes  3 , Sabrina Boyrie  1 , Perrine Dahan  1 , Nicolas Skuli  1   4 , Julie Sesen  1 , Thomas Filleron  3 , Aline Kowalski-Chauvel  1 , Elizabeth Cohen-Jonathan Moyal  1   5 , Christine Toulas  1   6 , Anthony Lemarié  1   2
Affiliations
Review

Interest of integrins targeting in glioblastoma according to tumor heterogeneity and cancer stem cell paradigm: an update

Laure Malric et al. Oncotarget. .

Abstract

Glioblastomas are malignant brain tumors with dismal prognosis despite standard treatment with surgery and radio/chemotherapy. These tumors are defined by an important cellular heterogeneity and notably contain a particular subpopulation of Glioblastoma-initiating cells, which recapitulate the heterogeneity of the original Glioblastoma. In order to classify these heterogeneous tumors, genomic profiling has also been undertaken to classify these heterogeneous tumors into several subtypes. Current research focuses on developing therapies, which could take into account this cellular and genomic heterogeneity. Among these targets, integrins are the subject of numerous studies since these extracellular matrix transmembrane receptors notably controls tumor invasion and progression. Moreover, some of these integrins are considered as membrane markers for the Glioblastoma-initiating cells subpopulation. We reviewed here integrin expression according to glioblastoma molecular subtypes and cell heterogeneity. We discussed their roles in glioblastoma invasion, angiogenesis, therapeutic resistance, stemness and microenvironment modulations, and provide an overview of clinical trials investigating integrins in glioblastomas. This review highlights that specific integrins could be identified as selective glioblastoma cells markers and that their targeting represents new diagnostic and/or therapeutic strategies.

Keywords: cancer stem cells; clinical trials; glioblastoma; integrins; targeted therapy.

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Conflict of interest statement

CONFLICTS OF INTEREST None.

Figures

Figure 1
Figure 1. Overview of main GIC properties
Figure 2
Figure 2. Overview of main integrin heterodimers and ligands
Figure 3
Figure 3. Integrins overexpression association with poor prognosis in GB patients
Kaplan-Meier survival plots were established using TCGA Affymetrix dataset (n = 184). Hazard ratios (HR) and p-values were given for univariate analyses. Adjusted HR and p-values were calculated for multivariate analyses, in relation to other prognostic clinical covariates (Age, G-CIMP status and Karnofsky score).
Figure 4
Figure 4. Main integrins expression in GB samples according to molecular subtypes
Plots were established using TCGA Affymetrix dataset (n = 500). *p ≤ 0.05; ** p ≤ 0.01; ***p ≤ 0.001. When not stated, values are compared to the “normal” subgroup.
Figure 5
Figure 5. Overview of integrin interactions with glioblastoma microenvironment and niches
See this image and copyright information in PMC

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