Human astrocytes secrete IL-6 to promote glioma migration and invasion through upregulation of cytomembrane MMP14

被引:76
作者
Chen, Weiliang [1 ,2 ,3 ,4 ]
Xia, Tongliang [1 ,2 ,3 ,4 ]
Wang, Donghai [2 ,3 ]
Huang, Bin [2 ,3 ]
Zhao, Peng [2 ,3 ]
Wang, Jian [2 ,3 ,5 ]
Qu, Xun [6 ]
Li, Xingang [2 ,3 ]
机构
[1] Shandong Univ, Qilu Hosp, Dept Otolaryngol, Jinan, Peoples R China
[2] Shandong Univ, Qilu Hosp, Dept Neurosurg, Jinan, Peoples R China
[3] Shandong Univ, Brain Sci Res Inst, Jinan, Peoples R China
[4] Chinese Minist Hlth, Key Lab Otolaryngol, Jinan, Peoples R China
[5] Univ Bergen, Dept Biomed, Bergen, Norway
[6] Shandong Univ, Qilu Hosp, Inst Basic Med Sci, Jinan, Peoples R China
基金
中国国家自然科学基金;
关键词
astrocytes; glioma; invasion; IL-6; MMP14; HUMAN HEPATOCELLULAR-CARCINOMA; BREAST-CANCER; CELL INVASION; TUMOR; GLIOBLASTOMA; GROWTH; TUMORIGENESIS; COMMUNICATION; CONCOMITANT; METASTASIS;
D O I
10.18632/oncotarget.11515
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
The brain microenvironment has emerged as an important component in malignant progression of human glioma. However, astrocytes, the most abundant glial cells in the glioma microenvironment, have as yet a poorly defined role in the development of this disease, particularly with regard to invasion. Here, we co-cultured human astrocytes with human glioma cell lines, U251 and A172, in an in vitro transwell system in order to ascertain their influence on migration and invasion of gliomas. mRNA and protein expression assays were subsequently used to identify candidate proteins mediating this activity. Astrocytes significantly increased migration and invasion of both U251 and A172 cells in migration and invasion (plus matrigel) assays. Membrane type 1 matrix metalloproteinase (MMP14) originating from glioma cells was identified in qRT-PCR as the most highly up-regulated member of the MMP family of genes (similar to 3 fold, p < 0.05) in this system. A cytokine array and ELISA were used to identify interleukin-6 (IL-6) as a highly increased factor in media collected from astrocytes, especially under co-culture conditions. IL-6 was also the key cytokine inducing cytomembrane MMP14 expression, the active form of MMP14, in glioma cells. Knockdown of MMP14 with siRNA led to decreased migration and invasion. Taken together, our results indicated that cytomembrane MMP14 was induced by IL-6 secreted from astrocytes, thereby enhancing the migration and invasion of glioma cells through activation of MMP2. Therefore, this IL-6 and MMP14 axis between astrocytes and glioma cells may become a potential target for treatment of glioma patients.
引用
收藏
页码:62425 / 62438
页数:14
相关论文
共 40 条
[1]
The brain tumor microenvironment (vol 59, pg 1169, 2011) [J].
Charles, Nikki A. ;
Holland, Eric C. ;
Gilbertson, Richard ;
Glass, Rainer ;
Kettenmann, Helmut .
GLIA, 2012, 60 (03) :502-514
[2]
Glioma cells escaped from cytotoxicity of temozolomide and vincristine by communicating with human astrocytes [J].
Chen, Weiliang ;
Wang, Donghai ;
Du, Xinwen ;
He, Ying ;
Chen, Songyu ;
Shao, Qianqian ;
Ma, Chao ;
Huang, Bin ;
Chen, Anjing ;
Zhao, Peng ;
Qu, Xun ;
Li, Xingang .
MEDICAL ONCOLOGY, 2015, 32 (03)
[3]
Epigenetic Control of the Invasion-promoting MT1-MMP/MMP-2/TIMP-2 Axis in Cancer Cells [J].
Chernov, Andrei V. ;
Sounni, Nor Eddine ;
Remacle, Albert G. ;
Strongin, Alex Y. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (19) :12727-12734
[4]
Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) promotes glioma cell invasion through induction of NF-κB-inducing kinase (NIK) and noncanonical NF-κB signaling [J].
Cherry, Evan M. ;
Lee, Dong W. ;
Jung, Ji-Ung ;
Sitcheran, Raquel .
MOLECULAR CANCER, 2015, 14
[5]
Cell type specific interleukin-6 induced responses in tumor keratinocytes and stromal fibroblasts are essential for invasive growth [J].
Depner, Sofia ;
Lederle, Wiltrud ;
Gutschalk, Claudia ;
Linde, Nina ;
Zajonz, Alexandra ;
Mueller, Margareta M. .
INTERNATIONAL JOURNAL OF CANCER, 2014, 135 (03) :551-562
[6]
New functions for the matrix metalloproteinases in cancer progression [J].
Egeblad, M ;
Werb, Z .
NATURE REVIEWS CANCER, 2002, 2 (03) :161-174
[7]
Cancer Invasion and the Microenvironment: Plasticity and Reciprocity [J].
Friedl, Peter ;
Alexander, Stephanie .
CELL, 2011, 147 (05) :992-1009
[8]
Cost of migration: Invasion of malignant gliomas and implications for treatment [J].
Giese, A ;
Bjerkvig, R ;
Berens, ME ;
Westphal, M .
JOURNAL OF CLINICAL ONCOLOGY, 2003, 21 (08) :1624-1636
[9]
Insulin-like growth factor binding protein-3 inhibits migration of endometrial cancer cells [J].
Gribben, Lujia ;
Baxter, Robert C. ;
Marsh, Deborah J. .
CANCER LETTERS, 2012, 317 (01) :41-48
[10]
The tumorigenic and angiogenic effects of MGSA/GRO proteins in melanoma [J].
Haghnegahdar, H ;
Du, JG ;
Wang, DZ ;
Strieter, RM ;
Burdick, MD ;
Nanney, LB ;
Cardwell, N ;
Luan, J ;
Shattuck-Brandt, R ;
Richmond, A .
JOURNAL OF LEUKOCYTE BIOLOGY, 2000, 67 (01) :53-62