Receptor-driven invasion profiles in diffuse intrinsic pontine glioma
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Updated: Nov 5, 2025
A Protocol for Rapid Post-mortem Cell Culture of Diffuse Intrinsic Pontine Glioma DIPG
Published on: March 7, 2017
Anju Karki1, Noah E Berlow1, Jin-Ah Kim1
1Children's Cancer Therapy Development Institute, Beaverton, Oregon, USA.
Background:
Diffuse intrinsic pontine glioma (DIPG) is a devastating pediatric cancer with unmet clinical need. DIPG is invasive in nature, where tumor cells interweave into the fiber nerve tracts of the pons making the tumor unresectable. Accordingly, novel approaches in combating the disease are of utmost importance and receptor-driven cell invasion in the context of DIPG is under-researched area. Here, we investigated the impact on cell invasion mediated by PLEXINB1, PLEXINB2, platelet growth factor receptor (PDGFR)α, PDGFRβ, epithelial growth factor receptor (EGFR), activin receptor 1 (ACVR1), chemokine receptor 4 (CXCR4), and NOTCH1.
Methods:
We used previously published RNA-sequencing data to measure gene expression of selected receptors in DIPG tumor tissue versus matched normal tissue controls (n = 18). We assessed protein expression of the corresponding genes using DIPG cell culture models. Then, we performed cell viability and cell invasion assays of DIPG cells stimulated with chemoattractants/ligands.
Results:
RNA-sequencing data showed increased gene expression of receptor genes such as PLEXINB2, PDGFRα, EGFR, ACVR1, CXCR4, and NOTCH1 in DIPG tumors compared to the control tissues. Representative DIPG cell lines demonstrated correspondingly increased protein expression levels of these genes. Cell viability assays showed minimal effects of growth factors/chemokines on tumor cell growth in most instances. Recombinant SEMA4C, SEM4D, PDGF-AA, PDGF-BB, ACVA, CXCL12, and DLL4 ligand stimulation altered invasion in DIPG cells.
Conclusions:
We show that no single growth factor-ligand pair universally induces DIPG cell invasion. However, our results reveal a potential to create a composite of cytokines or anti-cytokines to modulate DIPG cell invasion.
Insights
Diffuse intrinsic pontine glioma (DIPG) cell invasion is influenced by multiple receptor pathways. Targeting combinations of cytokines may offer a novel therapeutic strategy for this pediatric cancer.
Area of Science:
- Oncology
- Pediatric Cancer Research
- Molecular Biology
Background:
- Diffuse intrinsic pontine glioma (DIPG) is an aggressive pediatric brain tumor characterized by diffuse infiltration of pontine nerve tracts, rendering it unresectable.
- The invasive nature of DIPG presents a significant clinical challenge, necessitating research into novel therapeutic strategies.
- Receptor-mediated cell invasion in DIPG remains an under-researched area critical for understanding tumor progression.
Purpose of the Study:
- To investigate the role of specific receptor genes (PLEXINB1, PLEXINB2, PDGFRα, PDGFRβ, EGFR, ACVR1, CXCR4, NOTCH1) in mediating DIPG cell invasion.
- To assess the impact of various growth factors and chemokines on DIPG cell viability and invasion.
Main Methods:
- Analysis of RNA-sequencing data from DIPG tumor tissues and matched normal controls to determine gene expression levels of selected receptors.
- Assessment of corresponding protein expression in DIPG cell culture models.
- Conducting cell viability and invasion assays using DIPG cells stimulated with specific chemoattractants/ligands.
Main Results:
- Increased gene expression of PLEXINB2, PDGFRα, EGFR, ACVR1, CXCR4, and NOTCH1 was observed in DIPG tumors compared to controls.
- DIPG cell lines exhibited corresponding increases in protein expression for these receptors.
- While most growth factors/chemokines had minimal impact on cell viability, specific ligand stimulation (SEMA4C, SEM4D, PDGF-AA, PDGF-BB, ACVA, CXCL12, DLL4) significantly altered DIPG cell invasion.
Conclusions:
- No single growth factor-ligand pair universally drives DIPG cell invasion.
- The findings suggest a potential therapeutic strategy involving combinations of cytokines or anti-cytokines to modulate DIPG cell invasion.
- This research opens avenues for developing targeted therapies against DIPG by manipulating receptor-mediated invasion pathways.
