Matrix Metalloproteinase 11 Is a Potential Therapeutic Target in Lung Adenocarcinoma

Haoran Yang; Peng Jiang; Dongyan Liu; Hong-Qiang Wang; Qingmei Deng; Xiaojie Niu; Li Lu; Haiming Dai; Hongzhi Wang; Wulin Yang

doi:10.1016/j.omto.2019.03.012

Matrix Metalloproteinase 11 Is a Potential Therapeutic Target in Lung Adenocarcinoma

Mol Ther Oncolytics. 2019 Apr 6:14:82-93. doi: 10.1016/j.omto.2019.03.012. eCollection 2019 Sep 27.

Authors

Haoran Yang^{1

2

3}, Peng Jiang^{1

2

3}, Dongyan Liu^{1

2

3}, Hong-Qiang Wang⁴, Qingmei Deng³, Xiaojie Niu⁵, Li Lu⁵, Haiming Dai^{1

3}, Hongzhi Wang^{1

3}, Wulin Yang^{1

3}

Affiliations

¹ Anhui Province Key Laboratory of Medical Physics and Technology, Center of Medical Physics and Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China.
² University of Science and Technology of China, Hefei 230026, China.
³ Cancer Hospital, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China.
⁴ Biological Molecular Information System Lab., Institute of Intelligent Machines, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China.
⁵ Department of Anatomy, Shanxi Medical University, Taiyuan 030024, China.

Abstract

Lung cancer is one of the leading causes of cancer-associated death, with the etiology largely unknown. The aim of this study was to identify key driver genes with therapeutic potentials in lung adenocarcinoma (LUAD). Transcriptome microarray data from four GEO datasets (GEO: GSE7670, GSE10072, GSE68465, and GSE43458) were jointly analyzed for differentially expressed genes (DEGs). Ontologic analysis showed that most of the upregulated DEGs enriched in collagen catabolic and fibril organization processes were regulated by matrix metalloproteinases (MMPs). Matrix metalloproteinase 11 (MMP11), the highest upregulated MMP family member in LUAD-transformed cells, acted in an autocrine manner and was significantly increased in sera of LUAD patients. MMP11 depletion severely impaired LUAD cell proliferation, migration, and invasion in vitro, in line with retarded tumor growth in xenograft models. Treatment of different human LUAD cell lines with anti-MMP11 antibody significantly retarded cell growth and migration. Administration of anti-MMP11 antibody at a dose of 1 μg/g body weight significantly suppressed tumor growth in xenograft models. These findings indicate that MMP11 is a key cancer driver gene in LUAD and is an appealing target for antibody therapy.

Keywords: MMP11; antibody therapy; invasion; lung adenocarcinoma; migration; tumor growth.