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

Emmanuel J. Silva, Prokopios P. Argyris, Xiangqiong Zou, Karen F. Ross, Mark C. Herzberg

Research output: Contribution to journalArticlepeer-review

24 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)279-287
Number of pages9
JournalInternational Journal of Biochemistry and Cell Biology
StatePublished - Oct 2014

Bibliographical note

Funding Information:
This work was supported by NIH/NIDCR R01DE021206 to MCH and by CAPES 6177/11-5 to EJS. These studies were performed by EJS to satisfy partial requirements for the PhD degree at the Piracicaba School of Dentistry, University of Campinas, SP, Brazil.


  • Calprotectin
  • Carcinoma
  • In vitro
  • Matrix metalloproteinase-2
  • S100A8/A9


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