PUBLICATION
Ablation of neuropilin-1 improves the therapeutic response in conventional drug-resistant glioblastoma multiforme
- Authors
- Angom, R.S., Mondal, S.K., Wang, F., Madamsetty, V.S., Wang, E., Dutta, S.K., Gulani, Y., Sarabia-Estrada, R., Sarkaria, J.N., Quiñones-Hinojosa, A., Mukhopadhyay, D.
- ID
- ZDB-PUB-201003-8
- Date
- 2020
- Source
- Oncogene 39(48): 7114-7126 (Journal)
- Registered Authors
- Angom, Ramcharan Singh, Dutta, Shamit, Wang, Enfeng
- Keywords
- none
- MeSH Terms
-
- Animals
- Cell Line, Tumor
- Cell Movement/genetics
- Cell Proliferation/genetics
- Cell Transformation, Neoplastic
- Drug Resistance, Neoplasm/genetics*
- Gene Knockdown Techniques*
- Glioblastoma/drug therapy*
- Glioblastoma/genetics*
- Glioblastoma/pathology
- Humans
- Mice
- Neuropilin-1/deficiency*
- Neuropilin-1/genetics*
- Phenotype
- Survival Analysis
- Vascular Endothelial Growth Factor A/metabolism
- PubMed
- 33005016 Full text @ Oncogene
Citation
Angom, R.S., Mondal, S.K., Wang, F., Madamsetty, V.S., Wang, E., Dutta, S.K., Gulani, Y., Sarabia-Estrada, R., Sarkaria, J.N., Quiñones-Hinojosa, A., Mukhopadhyay, D. (2020) Ablation of neuropilin-1 improves the therapeutic response in conventional drug-resistant glioblastoma multiforme. Oncogene. 39(48):7114-7126.
Abstract
Glioblastoma multiforme (GBM) is a highly proliferative and locally invasive cancer with poor prognosis and a high recurrence rate. Although anti-VEGF (vascular endothelial growth factor) therapy offers short-term benefit to GBM patients, this approach fails as the tumor develops into a more invasive and drug-resistant phenotype and ultimately recurs. Recently, both glioma stemlike cells (GSCs) and brain tumor-initiating cells (BTICs) have been implicated in GBM recurrence and its resistance to therapy. We observed that patient-derived GBM cells expressing shRNAs of VEGF or neuropilin-1 (NRP-1) attenuate cancer stem cell markers, inhibit the tumor-initiating cell's neurosphere-forming capacity, and migration. Furthermore, both VEGF and NRP-1 knockdown inhibit the growth of patient-derived GBM xenografts in both zebrafish and mouse models. Interestingly, NRP-1-depleted patient-derived GBM xenografts substantially prolonged survival in mice compared to that of VEGF depletion. Our results also demonstrate that NRP-1 ablation of patient-derived GBM cells improves the sensitivity of TMZ and enhances the overall survival of the respective tumor-bearing mice. This improved outcome may provide insight into the inhibition of GBM progression and effective treatment strategies by targeting NRP-1 in addition to chemotherapy and radiotherapy.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping