Proteomic Analysis of Glioma Chemoresistance

Kyoungho Suk

doi:10.2174/157015912799362733

Abstract

Malignant glioma is the most common and destructive form of primary brain tumor. Along with surgery and radiation, chemotherapy remains as the major treatment modality. The emergence of drug resistance, however, often leads to a therapeutic failure in the treatment of glioma, precluding long-term survival of the patients. A proteomic approach has recently been adapted for the mechanistic analysis of glioma drug resistance. The proteomic analysis of drug-resistant glioma led to the discovery of novel biomarkers that can be used for the prognosis of glioma as well as for monitoring the drug response or resistance of glioma. These proteomics-based biomarkers can also be a druggable target that one can exploit for successful glioma chemotherapy. In this review, recent reports on proteomic analysis of glioma from the perspective of chemoresistance are discussed with a focus on the proteome profiles of glioma cells that are resistant to the alkylating agent, 1, 3-bis (2-chloroethyl)-1-nitrosourea (BCNU), as a prime example. Among numerous proteins that were up- or down-regulated in drug-resistant glioma cells, lipocalin 2 (LCN2) and integrin β3 (ITGB3) were identified as key proteins that determine the survival and death of glioma cells. LCN2, ITGB3, and other proteins identified by proteomic analysis could be utilized to overcome glioma chemoresistance.

Highlights

Glioma is a type of tumor that arises from glial cells in the central nervous system (CNS) [1]
15/22 4/30 314/515 2/29 31/60 0/10 21/40 4/12 14/19 33/56 15/20 3/11 14/18 effects of lipocalin 2 (LCN2). These results suggest that LCN2 protein may be involved in glioma drug resistance
With a recent interest in moving toward an integrative, rather than reductionist, approach to glioma biology in the post-genomic era, proteomic pattern comparisons between normal and glioma tissues of different grades led to the discovery of numerous potential biomarkers that could be translated into diagnosis or prognosis in the clinical field

Summary

INTRODUCTION

Glioma is a type of tumor that arises from glial cells in the central nervous system (CNS) [1]. A two-dimensional chromatography system was used to search for protein biomarkers of drug response in glioma Another similar study defined the proteomic profile of glioblastoma cells exposed to terpyridineplatinum(II) complexes (TPCs), a potent and specific inhibitor of human selenoprotein thioredoxin reductase (TrxR) [26]. Proteomic profiling in fetal human astrocytes and human glioblastoma cell lines U87MG and U87MG expressing type III EGFR deletion was followed by Western blot, ELISA, or RT-PCR in cell extracts and in tumor tissues to discover potential biomarkers like Hsp, major vault protein, tissue transglutaminase, and cystatin B. These results point to the advantages and limitations of cell culture studies.

C6-BCNU-R1

CONCLUSIONS