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.
Zhao
Ping
P
Nanjing Medical University Cancer Center, Key Laboratory of Antibody Technology of Ministry of Health, Nanjing, China.
Gao
Chongfeng
C
Dykema
Karl
K
Furge
Kyle
K
Feng
Zhenqing
Z
Cao
Brian
B
D016475:3T3 Cells; D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology*; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004285:Dogs; D004797:Enzyme-Linked Immunosorbent Assay; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000276:immunology; D005909:Glioblastoma / Q000473:pathology*; D006493:Heparin / Q000494:pharmacology; D017228:Hepatocyte Growth Factor / Q000276:immunology* / Q000494:pharmacology*; D006801:Humans; D007668:Kidney / Q000166:cytology; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014183:Transplantation, Heterologous
D057134:Antibodies, Neutralizing; D017228:Hepatocyte Growth Factor; D006493:Heparin