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

Zhao, Ping; Gao, Chongfeng; Dykema, Karl; Furge, Kyle; Feng, Zhenqing; Cao, Brian

doi:10.1016/j.canlet.2009.10.014

« Previous Next »Cancer Letters
Volume 291, Issue 2 , Pages 209-216, 28 May 2010

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

Ping Zhao
- Nanjing Medical University Cancer Center, Key Laboratory of Antibody Technology of Ministry of Health, Nanjing, China
- Van Andel Research Institute, Grand Rapids, MI, USA
Chongfeng Gao
- Van Andel Research Institute, Grand Rapids, MI, USA
Karl Dykema
- Van Andel Research Institute, Grand Rapids, MI, USA
Kyle Furge
- Van Andel Research Institute, Grand Rapids, MI, USA
Zhenqing Feng
- Nanjing Medical University Cancer Center, Key Laboratory of Antibody Technology of Ministry of Health, Nanjing, China
- Corresponding authors. Addresses: Van Andel Institute, 333 Bostwick Ave., NE, Grand, Rapids, MI 49503, USA. Tel.: +1 616 234 5342; fax: +1 616 234 5343 (B. Cao), Department of Pathology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, China. Tel.: +86 25 8686 2011 (Z. Feng).
Brian Cao
- Nanjing Medical University Cancer Center, Key Laboratory of Antibody Technology of Ministry of Health, Nanjing, China
- Van Andel Research Institute, Grand Rapids, MI, USA
- Corresponding authors. Addresses: Van Andel Institute, 333 Bostwick Ave., NE, Grand, Rapids, MI 49503, USA. Tel.: +1 616 234 5342; fax: +1 616 234 5343 (B. Cao), Department of Pathology, Nanjing Medical University, 140 Hanzhong Road, Nanjing, Jiangsu 210029, China. Tel.: +86 25 8686 2011 (Z. Feng).

Received 16 July 2009; received in revised form 9 October 2009; accepted 19 October 2009. published online 12 November 2009.

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.

Keywords: Glioblastoma multiforme, HGF, Neutralizing antibody, Xenograft, Heparin