Receptor Variant III

Abstract: The relationship between mutated proteins and the cancer stem cell population is unclear. Glioblastoma tumors frequently express EGFRvIII, an EGFR variant that arises via gene rearrangement and amplification. However, expression of EGFRvIII is restricted despite the prevalence of the alteration. Here we show that EGFRvIII is highly co-expressed with CD133 and that EGFRvIII + /CD133 + defines the population of cancer stem cells with the highest degree of self-renewal and tumor initiating ability. EGFRvIII + cells are associated with other stem/progenitor markers while markers of differentiation are found in EGFRvIII - cells. EGFRvIII expression is lost in standard cell culture but its expression is maintained in tumor sphere culture, and cultured cells also retain the EGFRvIII + /CD133 + co-expression and self-renewal and tumor initiating abilities. Elimination of the EGFRvIII + /CD133 + population using a bispecific antibody reduced tumorigenicity of implanted tumor cells better than any reagent directed against a single epitope. This work demonstrates that a mutated oncogene can have CSC specific expression and be used to specifically target this population.