Hypoxia promotes HO-8910PM ovarian cancer cell invasion via Snail-mediated MT1-MMP upregulation

被引:14
|
作者
Sun, Lijun [1 ]
Lin, Ping [2 ]
Qin, Zhuo [1 ]
Liu, Yusi [1 ]
Deng, Li-Li [3 ]
Lu, Changlian [1 ]
机构
[1] Harbin Med Univ, Coll Pharm, Dept Biopharmaceut Sci, Harbin 150081, Heilongjiang, Peoples R China
[2] Harbin Med Univ, Dept Biochem & Mol Biol, Harbin 150081, Heilongjiang, Peoples R China
[3] Harbin Med Univ, Affiliated Hosp 2, Dept Oncol, Harbin 150081, Heilongjiang, Peoples R China
基金
中国国家自然科学基金;
关键词
Hypoxia; ovarian cancer; Snail; three-dimensional extracellular matrix; membrane-type 1 matrix metalloproteinase; invasion; MESENCHYMAL STEM-CELLS; E-CADHERIN; MATRIX-METALLOPROTEINASE; EXTRACELLULAR-MATRIX; HEPATOMA-CELLS; EXPRESSION; MIGRATION; COLLAGEN; PROLIFERATION; OVEREXPRESSION;
D O I
10.1177/1535370215570205
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
The molecular mechanisms of ovarian cancer cell invasion under hypoxia remain unclear. Here we employed a 3D collagen model and chick chorioallantoic membrane (CAM) invasion assay to explore the influence of hypoxia on ovarian cancer cell invasion. Hypoxia (both 1% O-2 and CoCl2 150 and 250 mu M) induced HO-8910PM ovarian cancer cell invasion in 3D collagen and collagenolysis determined by hydroxyproline. Pretreatment with a hypoxia inducible factor-1 inhibitor, YC-1, or MMP inhibitor, GM6001, significantly inhibited 3D collagen invasion and degradation and cell proliferation. Hypoxia stimulated both mRNA and protein expressions of membrane-type 1 matrix metalloproteinase (MT1-MMP) and promoted MT1-MMP translocation to the cell surface in an YC-1 sensitive manner. MT1-siRNA transfection inhibited hypoxia-induced invasion, proliferation, and collagen degradation of cells in 3D collagen. Hypoxia stimulated Snail mRNA and protein expression as well as translocation to nucleus in an YC-1 sensitive manner. Overexpression of Snail with a recombinant plasmid in HO-8910PM cells resulted in an enhanced invasion in 3D collagen. Transfection with Snail-specific siRNA significantly decreased MT1-MMP expression and 3D collagen invasion. Hypoxia-treated cells significantly broke the upper CAM surface of 11-day-old chick embryos and infiltrated interstitial tissue, completely blocked in the presence of YC-1 or GM6001, or after MT1-MMP siRNA or Snail siRNA transfection. Together, these data suggest that hypoxia promotes HO-8910PM ovarian cancer cell traffic through 3D matrix via Snail-mediated MT1-MMP upregulation, a possible molecular mechanism of ovarian cancer cell invasion under hypoxia.
引用
收藏
页码:1434 / 1445
页数:12
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