Table 1 Summary of studies investigating CSC and TMZ
From: Chemoresistance of glioblastoma cancer stem cells - much more complex than expected
Author | serum free medium used? | Key findings (on TMZ and CSC) | Problems |
|---|---|---|---|
Eramo et al. (2006) | Yes | High resistance of neurosphere cultures to different drugs | No detailed investigation of stem cell properties. |
Liu et al. (2006) | Initial culture with serum | Differential susceptibility of CD133+ as compared to CD133- cells | No confirmation in vivo, non-physiological TMZ concentrations |
Clement et al. (2007) | Yes | Reduced clonogenicity by TMZ. | Study did not investigate TMZ effects in detail. |
Ghods et al. (2007) | No | Gliosarcoma cells grown as neurospheres were more resistant to TMZ than the same cells grown as monolayer. | Study did not control for different growth conditions (spheres vs. monolayer). |
Chua et al. (2008) | No | Increase of SP cell population after TMZ treatment. | No in vivo study on tumorigenicity, serum cultured cell lines (U87). |
Beier et al. (2008) | Yes | Depletion of clonogenic and tumorigenic cells by TMZ. | Only a few concentrations investigated. |
Bleau et al. (2009) | No (serum-free medium only for neurosphere experiments) | Increased tumorigenicity of glioma cell derived from murine glioma model after long term TMZ treatment (14d). First study that proved that TMZ may increase the tumorigenicity of gliomas. | Murine cells, no information on MGMT methylation status. |
Blough et al. (2010) | Yes | Susceptiblity of CSC lines dependent on MGMT expression and promoter status. | No detailed assessement of stem cell properties. |
Larmoral-Theys et al. (2010) | No | Decreased tumorigenicity of an oligodendroglial cell line after long-term TMZ treatment. | Serum cultured cell lines; no detailed assessment of stem cell properties. |
Glas et al. (2010) | Yes | Differential susceptibility of peripheral and central CSC lines to TMZ. No constant difference between central and peripheral samples. | No systematic assessment of stem cell properties and MGMT status. Conflicting data to Pistolatto et al. |
Pistolatto et al. (2010) | Yes | Higher resistance of central, hypoxic CD133 CSC as compared to cells derived from the periphery due to increased MGMT expression. | No validation in a larger set of samples. Conflicting data to Glas et al. |
Mihaliak et al. (2010) | Yes | Initial reduction of neurosphere-like growth after TMZ challenge; recovery in 4/5 CSC lines. | No assessment of the MGMT status; only a few concentrations investigated. |
Gilbert et al. (2010) | Yes | Initial reduction of neurosphere-like growth after TMZ challenge; inhibition of neurosphere recovery using by NOTCH inhibition. | See comment on Milhaliak et al. |
Villalva et al. (2011) | Yes | Decreased clonogenicity after treatment with TMZ. | Study did not investigate TMZ effects in detail. |
Hsieh et al. (2010) | Yes | Activation of IGF or shh increases the resistance of CSC to TMZ. Differentiated CSC (with 10% serum) were more susceptible to acute TMZ toxicity than CSC lines. | No controls for different growth conditions (spheres vs. monolayer and serum vs. stem cell medium) mentioned. |