IGFBP-2 Signaling in Glioma Progression and Therapeutic Applications

Insulin-like growth factor binding protein-2 (IGFBP-2) has emerged as a critical mediator of glioma biology, exerting pleiotropic effects on tumour cell proliferation, invasion and microenvironmental interactions. Elevated IGFBP-2 expression is consistently observed in high-grade gliomas and correlates with poor patient survival. Mechanistically, IGFBP-2 promotes cell motility and extracellular matrix remodelling through direct binding to integrin receptors and activation of downstream kinases such as PI3K/AKT and STAT3. Beyond intrinsic effects on tumour cells, IGFBP-2 influences angiogenesis and vasculogenic mimicry, thereby facilitating adaptive vascular networks independent of endothelial cells. It also modulates immunosuppressive pathways, including upregulation of PD-L1 and recruitment of regulatory myeloid cells, which together attenuate anti-tumour immunity. These multifaceted roles have spurred the development of therapeutic strategies targeting IGFBP-2 expression or function. Approaches under investigation include RNA interference, CRISPR-based gene editing, modulation of upstream regulators such as RNA methyltransferases, and peptide or antibody inhibitors that disrupt key protein–protein interactions. Preclinical studies demonstrate that attenuation of IGFBP-2 signalling can restore tumour suppressor activity, inhibit oncogenic pathways, normalise tumour vasculature and enhance responsiveness to chemotherapy and immunotherapy. Collectively, this body of work positions IGFBP-2 as both a biomarker and a compelling target for novel glioma treatments with the potential to improve clinical outcomes.

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IGFBP-2 Signaling in Glioma Progression and Therapeutic Applications publication trend

The graph below shows the total number of articles in igfbp-2 signaling in glioma progression and therapeutic applications across all publications each year (not limited to Nature Index journals).

Technical terms

IGFBP-2: Insulin-like growth factor binding protein-2, a regulator of IGF signalling influencing cell proliferation, invasion and survival in glioma.

Vasculogenic mimicry: Formation of vessel-like channels by tumour cells to support blood flow independent of endothelial cells.

Long non-coding RNA (lncRNA) HOTAIRM1: A non-coding transcript implicated in epigenetic regulation and tumour progression via modulation of gene expression.

METTL3: An RNA methyltransferase catalysing N6-methyladenosine modification of RNAs, affecting their stability and function.

PTEN: A tumour suppressor lipid phosphatase that antagonises PI3K/AKT signalling to regulate cell growth and survival.

PI3K/AKT/mTOR pathway: A key intracellular signalling cascade promoting cell proliferation, metabolism and survival, often dysregulated in cancer.

Immunotherapy: Treatment that harnesses the immune system to recognise and eliminate cancer cells.

References

1. METTL3-mediated HOTAIRM1 promotes vasculogenic mimicry icontributionsn glioma via regulating IGFBP2 expression. Journal of Translational Medicine (2023).
2. SVIP reduces IGFBP-2 expression and inhibits glioblastoma progression via stabilizing PTEN. Cell Death Discovery (2024).
3. IGFBP2 from a novel copper metabolism-associated biomarker promoted glioma progression and response to immunotherapy. Frontiers in Immunology (2023).
4. An Interaction between Insulin-like Growth Factor-binding Protein 2 (IGFBP2) and Integrin α5 Is Essential for IGFBP2-induced Cell Mobility*. Journal of Biological Chemistry (2006).
5. IGFBP2 expression predicts IDH-mutant glioma patient survival. Oncotarget (2016).