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

Abstract 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-i...

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Bibliographic Details
Published in:Cancer letters 2010-05, Vol.291 (2), p.209-216
Main Authors: Zhao, Ping, Gao, Chongfeng, Dykema, Karl, Furge, Kyle, Feng, Zhenqing, Cao, Brian
Format: Article
Language:English
Subjects:
3T3 Cells
Animals
Antibodies, Neutralizing - pharmacology
Anticoagulants
Blotting, Western
Cancer
Cell Division - drug effects
Cell growth
Cell Line, Tumor
Dogs
Enzyme-Linked Immunosorbent Assay
Gene Expression Regulation, Neoplastic - drug effects
Gene Expression Regulation, Neoplastic - immunology
Glioblastoma - pathology
Glioblastoma multiforme
Hematology, Oncology and Palliative Medicine
Heparin
Heparin - pharmacology
Hepatocyte Growth Factor - immunology
Hepatocyte Growth Factor - pharmacology
HGF
Humans
Kidney - cytology
Medical prognosis
Mice
Mice, Nude
Neoplasm Transplantation
Neutralizing antibody
Rodents
Transplantation, Heterologous
Tumorigenesis
Tumors
Vascular endothelial growth factor
Xenograft
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Summary:Abstract 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.
ISSN:0304-3835
1872-7980
DOI:10.1016/j.canlet.2009.10.014