S100A8/A9 Regulates MMP-2 Expression and Invasion and Migration by Carcinoma Cells

Overview

Journal Int J Biochem Cell Biol

Publisher Elsevier

Specialties Biochemistry
Cell Biology

Date 2014 Sep 20

PMID 25236491

Citations 28

Authors

Emmanuel J Silva

Prokopios P Argyris

Xianqiong Zou

Karen F Ross

Mark C Herzberg

Affiliations

Soon will be listed here.

Abstract

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.

Citing Articles

Survival prediction in patients with head and neck squamous cell carcinoma and novel mechanistic insights of S100A8/A9.

Hu Y, He M, Han Y, Zeng L, Ma Z, Zou X Discov Oncol. 2024; 15(1):657.

PMID: 39546127 PMC: 11568106. DOI: 10.1007/s12672-024-01540-w.

S100a8/A9 proteins: critical regulators of inflammation in cardiovascular diseases.

Sun Y, Xu H, Gao W, Deng J, Song X, Li J Front Cardiovasc Med. 2024; 11:1394137.

PMID: 39175627 PMC: 11338807. DOI: 10.3389/fcvm.2024.1394137.

The functions and regulatory pathways of S100A8/A9 and its receptors in cancers.

Zhou H, Zhao C, Shao R, Xu Y, Zhao W Front Pharmacol. 2023; 14:1187741.

PMID: 37701037 PMC: 10493297. DOI: 10.3389/fphar.2023.1187741.

Integrative analysis of gene expression and DNA methylation to identify biomarkers of non-genital warts induced by low-risk human papillomaviruses infection.

Alghamdi M, Al-Eitan L, Tarkhan A Heliyon. 2023; 9(5):e16101.

PMID: 37215908 PMC: 10196596. DOI: 10.1016/j.heliyon.2023.e16101.

An integrated bioinformatics analysis of the S100 in head and neck squamous cell carcinoma.

Bai G, Yue S, You Y, Zhao J, Tian Z, Wang Y Transl Cancer Res. 2023; 12(4):717-731.

PMID: 37180672 PMC: 10174761. DOI: 10.21037/tcr-22-1353.

References

Neth P, Ries C, Karow M, Egea V, Ilmer M, Jochum M . The Wnt signal transduction pathway in stem cells and cancer cells: influence on cellular invasion. Stem Cell Rev. 2007; 3(1):18-29. DOI: 10.1007/s12015-007-0001-y. View

Kong J, Ding F, Zhou C, Wang X, Miao X, Wu M . Loss of myeloid-related proteins 8 and myeloid-related proteins 14 expression in human esophageal squamous cell carcinoma correlates with poor differentiation. World J Gastroenterol. 2004; 10(8):1093-7. PMC: 4656340. DOI: 10.3748/wjg.v10.i8.1093. View

Sorenson B, Khammanivong A, Guenther B, Ross K, Herzberg M . IL-1 receptor regulates S100A8/A9-dependent keratinocyte resistance to bacterial invasion. Mucosal Immunol. 2011; 5(1):66-75. PMC: 3476723. DOI: 10.1038/mi.2011.48. View

Li M, Rezakhanlou A, Chavez-Munoz C, Lai A, Ghahary A . Keratinocyte-releasable factors increased the expression of MMP1 and MMP3 in co-cultured fibroblasts under both 2D and 3D culture conditions. Mol Cell Biochem. 2009; 332(1-2):1-8. DOI: 10.1007/s11010-009-0167-5. View

Zhou C, Gao Y, Johnson N, Gao J . Immunoexpression of matrix metalloproteinase-2 and matrix metalloproteinase-9 in the metastasis of squamous cell carcinoma of the human tongue. Aust Dent J. 2010; 55(4):385-9. DOI: 10.1111/j.1834-7819.2010.01258.x. View

Gerlach R, Demacq C, Jung K, Tanus-Santos J . Rapid separation of serum does not avoid artificially higher matrix metalloproteinase (MMP)-9 levels in serum versus plasma. Clin Biochem. 2006; 40(1-2):119-23. DOI: 10.1016/j.clinbiochem.2006.10.007. View

Lu C, Yang J, Chiang J, Hour M, Amagaya S, Lu K . Inhibition of invasion and migration by newly synthesized quinazolinone MJ-29 in human oral cancer CAL 27 cells through suppression of MMP-2/9 expression and combined down-regulation of MAPK and AKT signaling. Anticancer Res. 2012; 32(7):2895-903. View

Ivanova T, Vinokurova S, Petrenko A, Eshilev E, Solovyova N, Kisseljov F . Frequent hypermethylation of 5' flanking region of TIMP-2 gene in cervical cancer. Int J Cancer. 2004; 108(6):882-6. DOI: 10.1002/ijc.11652. View

Pellikainen J, Ropponen K, Kataja V, Kellokoski J, Eskelinen M, Kosma V . Expression of matrix metalloproteinase (MMP)-2 and MMP-9 in breast cancer with a special reference to activator protein-2, HER2, and prognosis. Clin Cancer Res. 2004; 10(22):7621-8. DOI: 10.1158/1078-0432.CCR-04-1061. View

10.

Sarkar S, Yong V . Inflammatory cytokine modulation of matrix metalloproteinase expression and invasiveness of glioma cells in a 3-dimensional collagen matrix. J Neurooncol. 2008; 91(2):157-64. DOI: 10.1007/s11060-008-9695-1. View

11.

Chen L, Xiao Z, Meng Y, Zhao Y, Han J, Su G . The enhancement of cancer stem cell properties of MCF-7 cells in 3D collagen scaffolds for modeling of cancer and anti-cancer drugs. Biomaterials. 2011; 33(5):1437-44. DOI: 10.1016/j.biomaterials.2011.10.056. View

12.

Ely M, Nees M, Karsai S, Magele I, Bogumil R, Vorderwulbecke S . Transcript and proteome analysis reveals reduced expression of calgranulins in head and neck squamous cell carcinoma. Eur J Cell Biol. 2005; 84(2-3):431-44. DOI: 10.1016/j.ejcb.2005.01.003. View

13.

Chen H, Yuan Y, Zhang C, Luo A, Ding F, Ma J . Involvement of S100A14 protein in cell invasion by affecting expression and function of matrix metalloproteinase (MMP)-2 via p53-dependent transcriptional regulation. J Biol Chem. 2012; 287(21):17109-17119. PMC: 3366841. DOI: 10.1074/jbc.M111.326975. View

14.

Sewell D, Yuan C, Robertson E . Proteomic signatures in laryngeal squamous cell carcinoma. ORL J Otorhinolaryngol Relat Spec. 2006; 69(2):77-84. DOI: 10.1159/000097406. View

15.

de Vicente J, Fresno M, Villalain L, Vega J, Hernandez Vallejo G . Expression and clinical significance of matrix metalloproteinase-2 and matrix metalloproteinase-9 in oral squamous cell carcinoma. Oral Oncol. 2005; 41(3):283-93. DOI: 10.1016/j.oraloncology.2004.08.013. View

16.

Schropfer A, Kammerer U, Kapp M, Dietl J, Feix S, Anacker J . Expression pattern of matrix metalloproteinases in human gynecological cancer cell lines. BMC Cancer. 2010; 10:553. PMC: 2964638. DOI: 10.1186/1471-2407-10-553. View

17.

Heizmann C, Fritz G, Schafer B . S100 proteins: structure, functions and pathology. Front Biosci. 2002; 7:d1356-68. DOI: 10.2741/A846. View

18.

Kulasekara K, Lukandu O, Neppelberg E, Vintermyr O, Johannessen A, Costea D . Cancer progression is associated with increased expression of basement membrane proteins in three-dimensional in vitro models of human oral cancer. Arch Oral Biol. 2009; 54(10):924-31. DOI: 10.1016/j.archoralbio.2009.07.004. View

19.

Roh M, Zheng Z, Kim H, Kwon J, Jeung H, Rha S . Differential expression patterns of MMPs and their role in the invasion of epithelial premalignant tumors and invasive cutaneous squamous cell carcinoma. Exp Mol Pathol. 2012; 92(2):236-42. DOI: 10.1016/j.yexmp.2012.01.003. View

20.

Nisapakultorn K, Ross K, Herzberg M . Calprotectin expression in vitro by oral epithelial cells confers resistance to infection by Porphyromonas gingivalis. Infect Immun. 2001; 69(7):4242-7. PMC: 98457. DOI: 10.1128/IAI.69.7.4242-4247.2001. View