Integrin Signaling and Therapeutic Strategies in Gliomas

Integrins are transmembrane receptors that mediate adhesion between glioma cells and the extracellular matrix, orchestrating signals that regulate proliferation, survival, invasion and angiogenesis. In gliomas, aberrant expression of specific α and β subunits contributes to aggressive growth and therapy resistance by activating focal adhesion kinase and PI3K/AKT pathways, modulating the tumour microenvironment and promoting vascular remodelling. Integrin engagement facilitates vasculogenic mimicry in glioblastoma, enabling tumour cells to form vessel-like networks independent of endothelial cells. Moreover, integrin-mediated signals cross-talk with growth factor receptors and immune checkpoints, influencing immune cell infiltration and therapeutic response. Recent advances exploit integrins as direct targets for peptides, antibodies and nanotherapeutics, aim to normalise tumour vasculature or deliver cytotoxic agents selectively across the blood–brain tumour barrier. These strategies seek to overcome the inherent invasiveness and recurrence of gliomas by disrupting key adhesion and survival pathways while enhancing delivery of conventional and emerging treatments.

Research from Nature Portfolio

A mesoscopic imaging workflow was developed to quantify changes in tumour vasculature and oxygenation in a murine glioma model. Light-sheet fluorescence microscopy combined with deep learning segmentation revealed that both cytotoxic and anti-angiogenic treatments predominantly induce vessel normalisation rather than regression, with only cytotoxic therapy alleviating hypoxia significantly. This quantitative approach clarifies mechanisms underlying vascular-targeted interventions and supports optimisation of combination regimens. In parallel, unbiased antigen screening identified integrin α2 as a novel nanotherapeutic target for glioblastoma. Comparative flow cytometry showed elevated α2 expression on tumour cells relative to normal glia. Antibody-directed liposomes carrying doxorubicin were engineered to exploit α2 specificity, achieving enhanced cytotoxicity in vitro and demonstrating ability to breach an in vitro blood–brain tumour barrier. These findings illustrate the potential of integrin-targeted delivery systems to improve chemotherapy localisation in glioma.

Integrin Signaling and Therapeutic Strategies in Gliomas publication trend

The graph below shows the total number of articles in integrin signaling and therapeutic strategies in gliomas across all publications each year (not limited to Nature Index journals).

Technical terms

Integrin: Heterodimeric protein complex that mediates cell adhesion to extracellular matrix and transmits signals regulating survival and migration.

Extracellular matrix: Network of proteins and polysaccharides surrounding cells that provides structural support and biochemical cues.

Vasculogenic mimicry: Process by which tumour cells form vessel-like channels to facilitate blood flow independent of endothelial cells.

Endoplasmic reticulum stress: Cellular condition arising when protein folding demand exceeds ER capacity, activating the unfolded protein response.

Blood–brain tumour barrier: Modified form of the blood–brain barrier around tumours that restricts drug penetration while allowing pathological vascular features.

Nanotherapeutic: Nanoscale delivery system engineered to target drugs to specific cells or tissues, improving efficacy and reducing off-target effects.

References

1. Integrin Signaling in Glioma Pathogenesis: From Biology to Therapy. International Journal of Molecular Sciences (2020).
2. Therapy-induced modulation of tumor vasculature and oxygenation in a murine glioblastoma model quantified by deep learning-based feature extraction. Scientific Reports (2024).
3. ITGA2 as a potential nanotherapeutic target for glioblastoma. Scientific Reports (2019).
4. Targeting Integrin α3 Blocks β1 Maturation, Triggers Endoplasmic Reticulum Stress, and Sensitizes Glioblastoma Cells to TRAIL-Mediated Apoptosis. Cells (2024).
5. αV-Integrin-Dependent Inhibition of Glioblastoma Cell Migration, Invasion and Vasculogenic Mimicry by the uPAcyclin Decapeptide. Cancers (2023).
6. ITGA1 Promotes Glioma Cell Proliferation and Affects Immune Cell Infiltration in Low‐Grade Glioma. Mediators of Inflammation (2024).