Figure 3.
Medulloblastoma exhibits a glycolytic phenotype that can be reversed by cyclopamine. (A) Quantitative real-time PCR analysis of HK2 and PKM2 mRNA expression in medulloblastoma from Math1-Cre/Ptcfl/fl mice (MB) compared to normal adult mice cerebella (Normal). *MB versus Normal, P < 0.05; n = 4. (B) Local L-lactate concentration in medulloblastoma from Math1-Cre/Ptcfl/fl mice compared to normal cerebella. Values are expressed as ng of lactate/mg of tissue. *MB versus Normal, P < 0.05 (C, D) MB neurospheres were incubated with 0.5 or 1 μM cyclopamine-KAAD for 48 hours and cell number was measured at the end of the treatment (C). HK2 and PKM2 mRNA levels were assessed in 1 μM Cyclopamine-KAAD treated cells (D). *P < 0.01 n = 4. (E) Cyclopamine-KAAD treatment (1 μM, 48 hours) decreases extracellular L-lactate levels in medulloblastoma cells cultures. Values were normalized for cell number and expressed as fold change relative to vehicle-treated values *Cyclopamine-KAAD versus control, P < 0.05, n = 3.