Interest of integrins targeting in glioblastoma according to tumor heterogeneity and cancer stem cell paradigm: an update
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Laure Malric1, Sylvie Monferran1,2, Julia Gilhodes3, Sabrina Boyrie1, Perrine Dahan1, Nicolas Skuli1,4, Julie Sesen1, Thomas Filleron3, Aline Kowalski-Chauvel1, Elizabeth Cohen-Jonathan Moyal1,5, Christine Toulas1,6 and Anthony Lemarié1,2
1INSERM U1037, Center for Cancer Research of Toulouse, Toulouse, France
2Faculty of Pharmaceutical Sciences, University of Toulouse III Paul Sabatier, Toulouse, France
3Department of Biostatistics, IUCT-Oncopole, Toulouse, France
4Department of Neurosurgery, Johns Hopkins University, Baltimore, Maryland, USA
5Department of Radiotherapy, IUCT-Oncopole, Toulouse, France
6Laboratory of Oncogenetic, IUCT-Oncopole, Toulouse, France
Anthony Lemarié, email: [email protected]
Keywords: glioblastoma, integrins, cancer stem cells, targeted therapy, clinical trials
Received: May 30, 2017 Accepted: July 23, 2017 Published: August 21, 2017
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.
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