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 and Anthony Lemarié 1, 2 1 INSERM U1037, Center for Cancer Research of Toulouse, Toulouse, France 2 Faculty of Pharmaceutical Sciences, University of Toulouse III Paul Sabatier, Toulouse, France 3 Department of Biostatistics, IUCT-Oncopole, Toulouse, France 4 Department of Neurosurgery, Johns Hopkins University, Baltimore, Maryland, USA 5 Department of Radiotherapy, IUCT-Oncopole, Toulouse, France 6 Laboratory of Oncogenetic, IUCT-Oncopole, Toulouse, France Correspondence to: Anthony Lemarié, email: anthony.lemarie@inserm.fr Keywords: glioblastoma, integrins, cancer stem cells, targeted therapy, clinical trials Received: May 30, 2017      Accepted: July 23, 2017      Published: August 21, 2017 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.