PT  - JOURNAL ARTICLE
AU  - Huang, Luping
AU  - Wang, Denian
AU  - Feng, Zhongxue
AU  - Zhao, Huan
AU  - Xiao, Fei
AU  - Wei, Yong'gang
AU  - Zhang, Heng
AU  - Li, Hongyu
AU  - Kong, Lingmiao
AU  - Li, Min
AU  - Liu, Fei
AU  - Zhang, Haili
AU  - Zhang, Wei
TI  - Inhibition of intermedin (adrenomedullin 2) suppresses the growth of glioblastoma and increases the antitumor activity of temozolomide
AID  - 10.1158/1535-7163.MCT-20-0619
DP  - 2020 Jan 01
TA  - Molecular Cancer Therapeutics
PG  - molcanther.0619.2020
4099  - http://mct.aacrjournals.org/content/early/2020/12/09/1535-7163.MCT-20-0619.short
4100  - http://mct.aacrjournals.org/content/early/2020/12/09/1535-7163.MCT-20-0619.full
AB  - Glioblastoma multiforme (GBM; grade IV glioma) is the most malignant type of primary brain tumor and is characterized by rapid proliferation and invasive growth. Intermedin (IMD) is an endogenous peptide belonging to the calcitonin gene-related peptide family and has been reported to play important roles in cell survival and invasiveness in several types of cancers. In this study, we found that the expression level of IMD was positively related to the malignancy grade of gliomas. The highest expression of IMD was found in GBM, indicating that IMD may play important roles in glioma malignancy. IMD increased the invasive ability of glioma cells by promoting filopodia formation, which is dependent on ERK1/2 activation. IMD-induced ERK1/2 phosphorylation also promoted GBM cell proliferation. In addition, IMD enhanced mitochondrial function and hypoxia-induced responses in GBM cells. Treatment with anti-IMD monoclonal antibodies not only inhibited tumor growth in both ectopic and orthotopic models of GBM but also significantly enhanced the antitumor activity of temozolomide (TMZ). Our study may provide novel insights into the mechanism of GBM cell invasion and proliferation and provide an effective strategy to improve the therapeutic effect of GBM treatments.