Response to Hypoxia is Variable Medulloblastoma

Eric Michael Thompson, MD1, Leslie Muldoon, PhD1, Edward Neuwelt, MD1

1Portland, OR United States

Keywords: medulloblastoma, brain tumor, molecular biology, gene, neuropathology

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       Medulloblastoma biology shows different phenotypes.
     The purpose of this project was to determine if hypoxia induces an aggressive phenotype in medulloblastoma cells that overexpress c-Myc (D283) and those that do not (DAOY) and to determine if targeting av integrins would prevent a hypoxia-induced aggressive phenotype.
     In this in vitro study, DAOY and D283 cells grown under hypoxic or normoxic conditions were treated with the anti-av integrin monoclonal antibody, intetumumab.
     Cell proliferation, migration, and expression of vascular endothelial growth factor (VEGF) were determined. Statistical significance was determined using ANOVA and non-paired t-tests.
     DAOY cells grown at 1% O2 had significantly higher rates of proliferation than those grown at 21% O2 (p<0.05). D283 cells did not have preferential growth at 1% or 21% O2. Both cells lines had a dose-dependent decrease in proliferation when treated with intetumumab, particularly at high concentration (1.5 mg/mL; p<0.05). DAOY and D283 cells had significantly less invasion in the presence of intetumumab when grown at 21% O2 (p<0.05). However, this decrease in invasion was not seen at 1% O2. DAOY cells grown at 1% O2 had significantly higher levels of VEGF than those grown at 21% O2 (p<0.01) while D283 cells did not. Intetumumab significantly decreased VEGF levels in DAOY cells at both O2 conditions (p<0.05) and in D283 cells at 21% O2 (p<0.01) but not 1% O2.
     This is an in vitro study.
     Intetumumab appears to decrease cell proliferation, invasion, and VEGF production preferentially under normoxic conditions.
     D283 cells did not increase proliferation or VEGF production in response to hypoxia compared to DAOY cells, further supporting the heterogenicity of medulloblastoma variants.


Project Roles:

E. Thompson (), L. Muldoon (), E. Neuwelt ()