Role of PDGFRα-mediated signalling in anoikis resistance in glioblastoma: in vitro study
Sneha Raut1, Meet Makwana1, Prakash Pillai2
1Division of Neurobiology, Department of Zoology, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, 390002, India.
Abstract:
Anoikis resistance, the evasion of programmed cell death when cells detach from the extracellular matrix (ECM), is a critical feature of glioblastoma (GBM) malignancy, contributing to tumor survival, spread, and resistance to therapy. We focused on the role of growth factor receptors, particularly platelet-derived growth factor receptor-α (PDGFRα), and integrin expression patterns in mediating this resistance. We first cultured cells under non-adherent conditions using polyHEMA-treated plates to induce anoikis resistance. We performed assays like cell survival, migration, and sphere formation. To delineate the role of PDGFRα signalling in anoikis resistance, we further employed pharmacological inhibitors of key signalling molecules such as AG1295 (PDGFRα blocker), HS173 (PI3K inhibitor), U0126 (ERK inhibitor), and AG490 (JAK-STAT inhibitor) which led to a decrease in cell survival, proliferation, and migration. These findings highlight the critical role of PDGFRα and associated signalling pathways in mediating anoikis resistance in GBM, offering potential therapeutic targets for intervention.
Insights
Glioblastoma cells evade programmed cell death (anoikis) through platelet-derived growth factor receptor-α (PDGFRα) signaling, promoting tumor growth and therapy resistance. Targeting PDGFRα and related pathways offers new therapeutic strategies for glioblastoma.
Area of Science:
- Oncology
- Cell Biology
- Molecular Medicine
Background:
- Anoikis resistance is a hallmark of glioblastoma (GBM) malignancy.
- This resistance contributes to tumor survival, metastasis, and therapeutic failure.
- Growth factor receptors and integrins are implicated in anoikis resistance.
Purpose of the Study:
- To investigate the role of platelet-derived growth factor receptor-α (PDGFRα) in mediating anoikis resistance in GBM.
- To explore the involvement of associated signaling pathways in this process.
Main Methods:
- GBM cells were cultured under non-adherent conditions to induce anoikis resistance.
- Assays included cell survival, migration, and sphere formation.
- Pharmacological inhibitors (AG1295, HS173, U0126, AG490) targeted PDGFRα and downstream signaling molecules.
Main Results:
- PDGFRα signaling was identified as critical for anoikis resistance in GBM.
- Inhibition of PDGFRα and associated pathways (PI3K, ERK, JAK-STAT) reduced cell survival, proliferation, and migration.
- Integrin expression patterns were also examined in relation to anoikis resistance.
Conclusions:
- PDGFRα signaling plays a pivotal role in GBM anoikis resistance.
- Targeting PDGFRα and its downstream pathways presents a promising therapeutic strategy for glioblastoma.
- Understanding these mechanisms can lead to novel interventions against GBM malignancy.
