Repeated hepatocyte growth factor neutralizing antibody treatment leads to HGF/SF unresponsiveness in human glioblastoma multiforme cells.

The purpose of this work is to seek putative markers for multi-targeted therapeutic treatment of human glioblastoma. We previously developed an anti-HGF neutralizing antibody cocktail Amix that inhibits human glioblastoma growth in mouse xenograft models. When these treated tumors were re-injected into nude mice and treatment with the neutralizing antibody cocktail plus heparin was repeated, the growth of the twice-treated tumors became HGF-independent, suggesting a possible switch in dominant signaling pathways. Microarray of the tumor cells revealed a number of genes elevated in the twice-treated tumor cells relative to untreated control tumors, including BAI1, CASP8, IL8, IGF1, TGFB1 and TNF. Our analyses provide a series of putative markers for additional evaluation in treating glioblastoma. Multi-targeted therapeutic approach might be a better solution for treating this disease.