We identified that CD44, ATP binding cassette subfamily C member 3 (ABCC3), and tumor necrosis factor receptor subfamily member 1A (TNFRSF1A) as highly expressed genes in GBMs are associated with patients' poor outcomes and therapy resistance.
Significance of Glioma Stem-Like Cells in the Tumor Periphery That Express High Levels of CD44 in Tumor Invasion, Early Progression, and Poor Prognosis in Glioblastoma.
We further show that the MES signature, CD44 expression, and NF-κB activation correlate with poor radiation response and shorter survival in patients with GBM.
In conclusion, our findings revealed that EMP3 might be a potential target for CD44-high GBMs and highlight the essential functions of EMP3 in TGF-β/Smad2/3 signaling activation and tumor progression.
Together, our results identify CD44 as a prime therapeutic target for GBM, establish potent antiglioma efficacy of CD44 antagonists, uncover a novel CD44 signaling pathway, and provide a first mechanistic explanation as to how upregulation of CD44 may constitute a key event in leading to cancer cell resistance to stresses of different origins.
Heparanase-expressing cells, including GBM tumor cells and neovessel endothelial cells, exhibited decreased expression of CD44, a cell adhesion molecule on the cell membrane that is important for regulating tumor invasion.
We found that the purified CD133+ GBM cells sorted from the CD133+ GBM spheres express SOX2 and CD44 and are capable of clonal self-renewal and dividing to produce fast-growing CD133- progeny, which form the major cell population within GBM spheres.
In summary, novel CD44 targeted polymeric based nanocarriers appear to be proficient in mediating site-specific delivery of quercetin via CD44 receptor in glioblastoma cells.
The results suggest that upregulation of NG2/CSPG4 rather than changes in CD44 or Ki-67 expression is associated with low overall survival in glioblastoma multiforme patients, supporting NG2/CSPG4 as a potential prognostic marker in glioblastoma.
Collectively, these findings advance our understanding of GBM biology by establishing tGLI1 as a novel transcriptional activator of CD44 and a novel mediator of mesenchymal GBM and GSC.<b>Significance:</b> These findings highlight the role of a tumor-specific gain-of-function transcription factor tGLI1 in mesenchymal glioma stem cell maintenance and mesenchymal GBM growth.<i></i>.
High levels of CD44 and DNA-PK are associated with a better survival and better response to radiotherapy and temozolomide and could establish prognosis classes by predicting survival and response to therapy for GBMs patients.
The present study investigated the expression of MIF and its functionally associated genes (D-DT, CD74, CD44, CXCR2 and CXCR4) in glioblastoma multiforme (GBM).
In the present study, CD44 isoform expression was evaluated by reverse transcriptase-polymerase chain reaction (PCR) analysis in frozen sections derived from three samples of normal brain tissue and from 40 brain tumors, including samples of glioblastoma multiforme, anaplastic astrocytoma, low-grade astrocytoma, cerebral primitive neuroectodermal tumor, medulloblastoma, metastatic colon carcinoma, and metastatic melanoma.
We also identify a role of extracellular HA (via CD44) in altering the effect of erlotinib in GBM EGFR + cells by modifying STAT3 phosphorylation status.
Overexpression of endogenous CD44 (cancer stem cell marker) promotes phosphorylation/inactivation of NF2, and upregulates YAP1 expression and leads to cancer cell resistance in glioblastoma.