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

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.

Tissue-guided LASSO for prediction of clinical drug response using preclinical samples

“…Another noteworthy GO term was integrin binding (FDR = 0.037). Integrins are transmembrane proteins that mediate cell adhesion, play an important role in promoting the invasiveness of glioma cells [48], and have been suggested as potential targets with diagnostic and prognostic value in glioma [49]. Several enriched GO terms were related to the activity of endopeptidases and collagen.…”

Spatial heterogeneity of cell-matrix adhesive forces predicts human glioblastoma migration

“…The failure of adhesion-block treatments may be due to the observed intra-and intertumoral heterogeneity, as typically preclinical tests use only one or two cell lines, which may not be representative of the distribution of integrin expression and adhesion in GBM tumors. Given that integrins play a crucial role in brain tumor infiltration 42 and GBM intratumor variability in integrin expressions 43 . New trials that aim to halt GBM recurrence by inhibiting radiation-induced invasion gains and signaling changes 11,44 , or kinase inhibitors 10 , could benefit from accounting for intra-and-intertumoral differences in single cell migration.…”

Targeting the complexity of Src signalling in the tumour microenvironment of pancreatic cancer: from mechanism to therapy

“…Several cancers, including glioblastoma, show modifications of the integrin pattern to be associated with tumour progression and poor patient survival, including a6b4, a6b1, avb6 and avb3 [119]. Several cancers, including glioblastoma, show modifications of the integrin pattern to be associated with tumour progression and poor patient survival, including a6b4, a6b1, avb6 and avb3 [119].…”

“…Integrins are key regulators of Src signalling, and are also deregulated in cancers, but are rarely mutated. Several cancers, including glioblastoma, show modifications of the integrin pattern to be associated with tumour progression and poor patient survival, including a6b4, a6b1, avb6 and avb3 [119]. An early sequencing study demonstrated a positive association between mutations in subunit a7 (encoded by ITGA7 gene), identified in 57% of prostate cancers, and increased cancer recurrence [120].…”