S100A8/A9 regulates MMP-2 expression and invasion and migration by carcinoma cells.

S100A8/A9 regulates MMP-2 expression and invasion and migration by carcinoma cells.
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DOI:
10.1016/j.biocel.2014.09.007
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发表时间:
2014-10
影响因子:
4
通讯作者:
Herzberg, Mark C.
Herzberg, Mark C.
中科院分区:
生物学2区
文献类型:
--
作者:
Silva, Emmanuel J.;Argyris, Prokopios P.;Zou, Xianqiong;Ross, Karen F.;Herzberg, Mark C.

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Intracellular calprotectin (S100A8/A9) functions in the control of the cell cycle checkpoint at G2/M. Dysregulation of S100A8/A9 appears to cause loss of the checkpoint, which frequently characterizes head and neck squamous cell carcinoma (HNSCC). In the present study, we analyzed carcinoma cells for other S100A8/A9-directed changes in malignant phenotype. Using a S100A8/A9-negative human carcinoma cell line (KB), transfection to express S100A8 and S100A9 caused selective down-regulation of MMP-2 and inhibited in vitro invasion and migration. Conversely, silencing of endogenous S100A8 and S100A9 expression in TR146 cells, a well-differentiated HNSCC cell line, increased MMP-2 activity and in vitro invasion and migration. When MMP-2 expression was silenced, cells appeared to assume a less malignant phenotype. To more closely model the architecture of cell growth in vivo, cells were grown in a 3D collagen substrate, which was compared to 2D. Growth on 3D substrates caused greater MMP-2 expression. Whereas hypermethylation of CpG islands occurs frequently in HNSCC, S100A8/A9-dependent regulation of MMP-2 could not be explained by modification of the upstream promoters of MMP2 or TIMP2. Collectively, these results suggest that intracellular S100A8/A9 contributes to the cancer cell phenotype by modulating MMP-2 expression and activity to regulate cell migration and mobility.
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