Differences in stem cell marker and osteopontin expression in primary and recurrent glioblastoma

Abstract

Background Despite of a multimodal approach, recurrences can hardly be prevented in glioblastoma. This may be in part due to so called glioma stem cells. However, there is no established marker to identify these stem cells. Methods Paired samples from glioma patients were analyzed by immunohistochemistry for expression of the following stem cell markers: CD133, Musashi, Nanog, Nestin, octamer-binding transcription factor 4 (Oct4), and sex determining region Y-box 2 (Sox2). In addition, the expression of osteopontin (OPN) was investigated. The relative number of positively stained cells was determined. By means of Kaplan–Meier analysis, a possible association with overall survival by marker expression was investigated. Results Sixty tissue samples from 30 patients (17 male, 13 female) were available for analysis. For Nestin, Musashi and OPN a significant increase was seen. There was also an increase (not significant) for CD133 and Oct4. Patients with mutated Isocitrate Dehydrogenase-1/2 (IDH-1/2) status had a reduced expression for CD133 and Nestin in their recurrent tumors. Significant correlations were seen for CD133 and Nanog between OPN in the primary and recurrent tumor and between CD133 and Nestin in recurrent tumors. By confocal imaging we could demonstrate a co-expression of CD133 and Nestin within recurrent glioma cells. Patients with high CD133 expression had a worse prognosis (22.6 vs 41.1 months, p = 0.013). A similar trend was seen for elevated Nestin levels (24.9 vs 41.1 months, p = 0.08). Conclusions Most of the evaluated markers showed an increased expression in their recurrent tumor. CD133 and Nestin were associated with survival and are candidate markers for further clinical investigation.

The addition of arginine deiminase potentiates Mithramycin A-induced cell death in patient-derived glioblastoma cells via ATF4 and cytochrome C

“…Stem cell factors, such as OCT-4 and NANOG, are critical for pluripotency and the ability to self-renew embryonic cells and are also thought to play a role in GBM development and recurrence [ 36 , 37 ]. A2B5 and GFAP are markers for neuroglial stem cells [ 38 ].…”

Cancer- related protein profile of patient-derived and commercial glioblastoma cell lines exposed to Temozolomide

“…This glycophosphoprotein modulates multiple mechanisms of tumor-mediated immune suppression and has a pivotal role at the crossroads of in ammation and tumor progression. OPN plays an important role in tumor reparing, processes of remodelling the extracellular matrix after injury and is also responsible for protumorigenic reprogramming of TAM [45]. In experimental studies, OPN de ciency was associated with reduced immune-suppressive activity of M2 macrophages and decreased OPN/CD44 signaling lead to promotion of aggressive tumor growth as a conseqeunce of enhancement of cancer stem cell activity in the glioma perivascular niche [46].…”

An Overview of CD133 as a Functional Unit of Prognosis and Treatment Resistance in Glioblastoma

“…As with the research field focused on resistance, recurrence has become another growing area of interest due to the affiliation of recurrence with CD133+ cells. Across studies, it has been identified that recurrent GBM has higher expressions of CD133 when compared to the initial tumors [ 27 ]. This is significant because it shows that there are more CSCs in the recurrent tumor, possibly due to the contribution of CD133.…”

“… Modified Sankey diagram sorting the publications used into publication type, year, and subgroup [ 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ]. …”