The effect of alpha-v integrin inhibition on the malignant characteristics of medulloblastoma.

TLDR: Targeting α(v) integrins with the monoclonal antibody intetumumab represents a promising potential adjuvant modality in the treatment of medulloblastoma, particularly subtypes that metastasize and overexpress VEGF and c-Myc.

Abstract: Object Hypoxia induces an aggressive phenotype in some brain tumors in part due to hypoxia-inducible factor–1α (HIF-1α) and integrin expression. The importance of hypoxia in medulloblastoma is unclear and the interaction of HIF-1α and c-Myc in medulloblastoma has not been explored. The objective of this study was to determine if hypoxia induces an aggressive phenotype in human medulloblastoma cells that constitutively express high (D283 Med) or low (DAOY) levels of c-Myc and to determine if blocking αv integrins with the monoclonal antibody intetumumab inhibits hypoxia-induced cellular stress responses. Methods Cells were grown at 21% and 1% O2 and in the presence or absence of intetumumab. Measures of malignancy evaluated included cell proliferation, cell migration, and expression of vascular endothelial growth factor (VEGF), αv integrins, HIF-1α, and c-Myc. Results Both cell lines robustly expressed αv integrins. Hypoxic DAOY cells showed significantly increased proliferation compared with normoxic cont...