Etiology and Pathogenesis > Invasion | Integrative Medicine > Boswellia  

Meeting Abstract

Increased expression of 5-lipoxygenase in glioblastoma multiforme

Mladen Golubic, Naren Nathoo, Richard A. Prayson, Linda Vargo, Judy Bondar, Susana Arrigain, Gene H. Barnett

Cleveland Clinic Foundation, Cleveland, OH

The cells of human astrocytomas contain elevated levels of arachidonic acid compared to normal brain tissue and overexpress cyclooxygenase-2 (COX-2). 
It is, however, not known whether another eicosanoid producing enzyme, 5-lipoxygenase (5-LO) is expressed in human astrocytomas and what effect its expression may have on patient outcome. 
Expression of 5-LO mRNA of surgical astrocytoma specimens and glioblastoma multiforme (GBM) cell lines was determined by reverse transcriptase-polymerase chain reaction. 
5-LO protein expression was assessed by immunoblotting of protein extracts prepared from surgical astrocytoma specimens and cell lines and by immunohistochemical analysis of frozen surgical specimens (13 low-grade astrocytomas, 10 anaplastic astrocytomas and 49 GBMs) by anti-5-LO antibody. 
Increased 5-LO mRNA and protein expression was detected in surgical astrocytoma specimens and established GBM cell lines compared with primary cell culture from the human white matter. 
Immunohistochemical analysis revealed predominantly nuclear 5-LO staining in 44 of 49 GBM (90%), 8 of 10 (80%) anaplastic astrocytomas and 3 of 13 (23%) low-grade astrocytoma samples analyzed. 
Double-staining experiments with anti-CD-68 (macrophage/microglial marker) and anti-5-LO antibodies suggest that both CD-68-positive (macrophages/microglia) and CD-68-negative tumor cells express 5-LO protein. 
Staining of 5-LO was significantly more frequent in high-grade than in the low-grade tumors (P<0.001). 
Patients whose tumors expressed 5-LO were significantly older, had lower pre-operative Karnofsky Perfomance Score (KPS) and shorter survival than patients whose tumors did not express 5-LO. 
After adjusting for pathologic diagnosis and age, respectively, KPS and survival were no longer significantly associated with 5-LO staining. 
This data indicates that 5-LO is overexpressed in high-grade astrocytomas and adds further support for the idea that eicosanoids may play a role in tumorigenesis and progression of these malignant brain tumors.

Copyright © 2003 American Association for Cancer Research. All rights reserved.