Mesenchymal/proangiogenic factor YKL-40 related to glioblastomas and its relationship with the subventricular zone

Abstract

A b s t r a c t

The adaptive transition of glioblastoma stem cells and its implications on treatments

“…109,110 Several studies reported that GSCs are derived from subventricular NSCs, [111][112][113] and the fact that by engineering p53, 114 EGFR 115 or H-Ras V12 88 in NSCs can induce the formation of GSCs. Gnomically, NSCs and GSCs share common gene signatures including SOX2, NESTIN, OLIG2, CD133, YKL40, et al 116,117 CD133 and Nestin are both expressed in B1 astrocytes and PN GSCs; EGFR is mainly enriched in type C cells and MES GSCs 118,119 (Table 3). This hallmark similarity implies the association between NSCs and GSCs.…”

Receptor tyrosine kinase targeting in glioblastoma: performance, limitations and future approaches

“…Among them, afatinib and dacomitinib were approved by the FDA. In 2015, a phase I/phase II study regarding afa- Imatinib showed no significant changes in the HGGs and especially GBM tumor growth [46] Better results were obtained in combination with hydroxyurea [47] Tandutinib had little effect [ Vatalanib enhances the antiangiogenic activity [54] Disappointing results were obtained for pazopanib in combination with lapatinib [57] No promising activity for GBM patients treated with sunitinib [58] Cediranib is an inhibitor of VEGFR, PDGFR, and c-kit [59] Thalidomide had a good effect as palliative drug in advanced secondary glioblastoma [60] Cabozantinib had good results both in vitro and in clinical trials [61,62] SU1498 had a limited anti-tumor activity [51] EGFR -epidermal growth factor receptor, PDGFR -platelet-derived growth factor receptor, IGF-R -insulin-like growth factor receptor, VEGFR -vascular endothelial growth factor receptor, FDA -Food and Drug Administration, ERK -extracellular signal-regulated kinases, HGGs -high-grade gliomas, GBs -glioblastomas, c-kittransmembrane tyrosine kinase receptor tinib alone or in combination with temozolomide proved that the drug was safe but with limited activity [37]. Also, single-agent dacomitinib proved to have limited activity in a phase II clinical trial in recurrent glioblastoma patients with EGFR amplification [38], following preclinical studies with good results [39].…”

“…YKL-40, a mesenchymal marker known as human cartilage glycoprotein-39 or chitinase-like protein 1, seems to have a key role in the motility and migrating features of glioma stem like cells and in their differentiation into endothelial cells, involved in angiogenesis [61]. It was proven that YKL-40 upregulates VEGF expression, and tumor vasculogenesis induced by YKL-40 is partially dependent on VEGF [62]; therefore therapies targeting YKL-40 may have potential benefit in GB treatment.…”

Targeting Glioblastoma Stem Cells: A Review on Biomarkers, Signal Pathways and Targeted Therapy

“…GBM is one of various tumors which highly expresses VEGF and its receptors, resulting in highly vascularized tumors and increased microvasculature compared to other normal tissues ( 162 ), and is an important target in glioblastoma aberrant VEGFR2 signaling, which is an important pathway affecting survival, proliferation, migration, and vessel permeability in tumor cells ( 163 ). Furthermore, it has recently been demonstrated that human cartilage glycoprotein-39 or chitinase-like protein-1 (YKL-40) may be effective targets, as they are able to upregulate VEGF expression and induce new tumor vasculature ( 164 ). There are a wide variety of VEGFR inhibitors (TKIs) with different treatment effects, including atalanib (PTK787), mainly against VEGFR2, PDGFR, and c-kit ( 165 ), sorafenib ( 166 ), tivozanib ( 167 ), pazopanib combined with lapatinib ( 168 ), Cediranib ( 169 ), and SU1498 ( 170 ).…”