Abstract
Simple SummaryLipocalin-2 (LCN2) exhibits pro- and anti-carcinogenic effects in several cancers, but its role in the progression of glioblastoma multiforme (GBM) remains poorly understood. We observed that the overexpression of LCN2 inhibits GBM cell proliferation and invasion via activation of ERK-induced CTSD expression. LCN2 overexpression may be a treatment strategy and prognostic marker for GBM.Lipocalin-2 (LCN2) exhibits pro- and anti-carcinogenic effects in several cancers, but its role in the progression of glioblastoma multiforme (GBM) remains unclear. This study aims to elucidate the effect of LCN2 in human GBM cell, and the mechanism underlying its effects on GBM malignant progression. We observed that LCN2 expression was significantly lower in GBM than in normal tissues and was associated with poorer GBM patient survival. LCN2-overexpressing GBM cells showed significantly reduced proliferation and migration/invasion abilities. Human protease antibody array analysis showed that the expression of cathepsin D (CTSD) protein and mRNA was lower in LCN2-overexpressing GBM cells than in controls. Higher CTSD expression was observed in GBM tumors than in normal tissues, and higher CTSD expression was associated with poorer overall and disease-free survival. LCN2-overexpressing GBM cells exhibited increased ERK phosphorylation. Treatment of these cells with a MEK inhibitor (U0126) restored CTSD expression, cell migration, and cell invasiveness. In conclusion, LCN2 might be serving as a prognostic marker and promising anti-proliferative and anti-metastatic target for treating GBM.
Highlights
This study investigates the effect of LCN2 in human glioblastoma multiforme (GBM) cells, its effects on tumorigenesis, and the mechanism underlying its effects on GBM malignant progression
To clarify the role of ERK/cathepsin D (CTSD) expression is LCN2induced effects on GBM8901 and U-251 cells, we investigated protein expression and overexpressing cells, using the knockdown assay to found that treatment of siRNA-CTSD
Our results found that migration and invasion significantly inhibition of si-Control-LCN2 or si-CTSD-Neo treatment upon LCN2 overexpressing GBM cells, but not completely inhibition of CTSD
Summary
Glioblastoma multiforme (GBM) is the most malignant and frequently occurring type of primary brain tumor [1]. Despite a variety of therapies against GBM including surgery with adjuvant chemo- or radiotherapy, the prognosis is still poor and survival is limited [2]. Recently-developed targeted therapies that are developed to overcome GBM resistance to chemo- or radio-therapy show promising results [3]. A better understanding of the mechanisms underlying GBM progression could promote the development of novel therapeutic choices for better patient outcomes
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