巨噬细胞移动抑制因子
卵巢癌
癌症研究
癌症
单克隆抗体
医学
体内
LNCaP公司
前列腺癌
细胞因子
阿霉素
顺铂
免疫学
胰腺癌
结直肠癌
细胞毒性T细胞
抗体
生物
内科学
体外
化疗
生物化学
生物技术
作者
Alexander Schinagl,Michael Thiele,Patrice Douillard,Dirk Völkel,Lukas Kenner,Zahra Kazemi,Michael Freissmuth,Friedrich Scheiflinger,Randolf J. Kerschbaumer
出处
期刊:Oncotarget
[Impact Journals, LLC]
日期:2016-09-12
卷期号:7 (45): 73486-73496
被引量:26
标识
DOI:10.18632/oncotarget.11970
摘要
Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine, which was shown to be upregulated in cancers and to exhibit tumor promoting properties. Unlike other cytokines, MIF is ubiquitously present in the circulation and tissue of healthy subjects. We recently described a previously unrecognized, disease-related isoform of MIF, designated oxMIF, which is present in the circulation of patients with different inflammatory diseases. In this article, we report that oxMIF is also linked to different solid tumors as it is specifically expressed in tumor tissue from patients with colorectal, pancreatic, ovarian and lung cancer. Furthermore, oxMIF can be specifically targeted by a subset of phage display-derived fully human, monoclonal anti-MIF antibodies (mAbs) that were shown to neutralize pro-tumorigenic activities of MIF in vivo. We further demonstrate that anti-oxMIF mAbs sensitize human cancer cell lines (LNCaP, PC3, A2780 and A2780ADR) to the action of cytotoxic drugs (mitoxantrone, cisplatin and doxorubicin) in vitro and in an A2780 xenograft mouse model of ovarian cancer. We conclude that oxMIF is the disease related isoform of MIF in solid tumors and a potential new diagnostic marker and drug target in cancer.
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