Advertisement

Tumor Biology

, Volume 35, Issue 12, pp 12535–12543 | Cite as

Increased expression levels of S100A4 associated with hypoxia-induced invasion and metastasis in esophageal squamous cell cancer

  • Xiaoyan Xuan
  • Qianru Li
  • Zhongning Zhang
  • Ying Du
  • Pingping Liu
Research Article

Abstract

Here, we explored the expression of S100A4 in esophageal squamous cell cancer (ESCC) tissues and investigated its role in hypoxia-induced invasion and metastasis in ESCC cell lines EC-1 and EC-9706. Immunohistochemistry analysis demonstrated that S100A4 was overexpressed in human ESCC tissues especially in ESCC tissues with deep invasion and lymph node metastasis. Hypoxia-induced S100A4 overexpression was observed in EC-1 and EC-9706 cells, in which it was associated with invasion and metastasis. Furthermore, we used EC-1 and EC-9706 cells again to upregulate or knockdown the expression S100A4 to investigate the mechanism role of S100A4 in hypoxia-induced invasion and metastasis in ESCC cells. And the results showed that S100A4 played an important role in promoting the invasion and metastasis of EC-1 and EC-9706 cells under hypoxia. Therefore, S100A4 overexpression might be an important mechanism by which hypoxia induced invasion and metastasis, and S100A4 could also be a potential target for the treatment of ESCC.

Keywords

Esophageal cancer S100A4 Hypoxia Invasion and metastasis 

Notes

Acknowledgments

We thank Prof. Li Shanshan and Dr. Wang Feng for retrieving the tumor specimens and performing the H&E staining and Prof. Du Xiantang for proofreading the manuscript.

Grant support

This work was supported by grants from the funding scheme for young teachers of Zhengzhou University.

References

  1. 1.
    Ji-Sheng L, Jian-Ming Y, Xiu-Wen W, Zhao-Hui W, Qian T, Li-Li L. Promoter methylation of tumor suppressor genes in esophageal squamous cell carcinoma. Chin J Cancer. 2013;32:3–11.CrossRefGoogle Scholar
  2. 2.
    Yuxin H, Correa AM, Ashraful H, Baoxiang G, Fei Y, Jie H, et al. Prognostic significance of differentially expressed miRNAs in esophageal cancer. Int J Cancer. 2011;128:132–43.CrossRefGoogle Scholar
  3. 3.
    Ismail TM, Zhang S, Fernig DG, Gross S, Martin-Fernandez ML, See V, et al. Self-association of calcium-binding protein S100A4 and metastasis. J Biol Chem. 2010;285:914–22.PubMedCentralPubMedCrossRefGoogle Scholar
  4. 4.
    Shuangping L, Leilei L, Yingyi Z, Yiwen Z, Yu Z, Xiaona Y, et al. The oncoprotein HBXIP uses two pathways to up-regulate S100A4 in promotion of growth and migration of breast cancer cells. J Biol Chem. 2012;287:30228–39.CrossRefGoogle Scholar
  5. 5.
    Takenaga K, Nakanishi H, Wada K, Suzuki M, Matsuzaki O, Matsuura A, et al. Increased expression of S100A4, a metastasis-associated gene, in human colorectal adenocarcinomas. Clin Cancer Res. 1997;3:2309–16.PubMedGoogle Scholar
  6. 6.
    Rudland PS, Platt-Higgins A, Renshaw C, West CR, Winstanley JH, Robertson L, et al. Prognostic significance of the metastasis-inducing protein S100A4 (p9Ka) in human breast cancer. Cancer Res. 2000;60:1595–603.PubMedGoogle Scholar
  7. 7.
    Pedersen KB, Nesland JM, Fodstad O, Maelandsmo GM. Expression of S100A4, E-cadherin, alpha- and beta-catenin in breast cancer biopsies. Br J Cancer. 2002;87:1281–6.PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Schuyer M, Henzen-Logmans SC, van der Burg ME, Fieret JH, Derksen C, Look MP, et al. Genetic alterations in ovarian borderline tumours and ovarian carcinomas. Eur J Obstet Gynecol Reprod Biol. 1999;82:147–50.PubMedCrossRefGoogle Scholar
  9. 9.
    Ito Y, Yoshida H, Tomoda C, Uruno T, Miya A, Kobayashi K, et al. S100A4 expression is an early event of papillary carcinoma of the thyroid. Oncol. 2004;67:397–402.CrossRefGoogle Scholar
  10. 10.
    Rosty C, Ueki T, Argani P, Jansen M, Yeo CJ, Cameron JL, et al. Overexpression of S100A4 in pancreatic ductal adenocarcinomas is associated with poor differentiation and DNA hypomethylation. Am J Pathol. 2002;160:45–50.PubMedCentralPubMedCrossRefGoogle Scholar
  11. 11.
    Kimura K, Endo Y, Yonemura Y, Heizmann CW, Schafer BW, Watanabe Y, et al. Clinical significance of S100A4 and E-cadherin-related adhesion molecules in non-small cell lung cancer. Int J Oncol. 2000;16:1125–31.PubMedGoogle Scholar
  12. 12.
    Takenaga K, Nakamura Y, Sakiyama S. Expression of antisense RNA to S100A4 gene encoding an S100-related calcium-binding protein suppresses metastatic potential of high-metastatic Lewis lung carcinoma cells. Oncogene. 1997;14:331–7.PubMedCrossRefGoogle Scholar
  13. 13.
    Ninomiya I, Ohta T, Fushida S, Endo Y, Hashimoto T, Yagi M, et al. Increased expression of S100A4 and its prognostic significance in esophageal squamous cell carcinoma. Int J Oncol. 2001;18:715–20.PubMedGoogle Scholar
  14. 14.
    Gupta S, Hussain T, MacLennan GT, Fu P, Patel J, Mukhtar H. Differential expression of S100A2 and S100A4 during progression of human prostate adenocarcinoma. J Clin Oncol. 2003;21:106–12.PubMedCrossRefGoogle Scholar
  15. 15.
    Dong C, Xue-Feng Z, Ze-You Y, Dong-Xiao L, Guo-You Z, Xue-Long J, et al. S100A4 silencing blocks invasive ability of esophageal squamous cell carcinoma cells. World J Gastroenterol. 2012;18:915–22.CrossRefGoogle Scholar
  16. 16.
    Hongyan C, Chengshan X, Qing’e J, Zhihua L. S100 protein family in human cancer. Am J Cancer Res. 2014;4:89–115.Google Scholar
  17. 17.
    Ruan K, Song G, Ouyang G. Role of hypoxia in the hallmarks of human cancer. J Cell Biochem. 2009;14(6):1053–62.CrossRefGoogle Scholar
  18. 18.
    Iovine B, Oliviero G, Garofalo M, Orefice M, Nocella F, Borbone N, et al. The anti-proliferative effect of L-carnosine correlates with a decreased expression of hypoxia inducible factor 1 alpha in human colon cancer cells. PLoS One. 2014;9:e96755.PubMedCentralPubMedCrossRefGoogle Scholar
  19. 19.
    Murielle M, Batra SK. Hypoxia-inducing factors as master regulators of stemness properties and altered metabolism of cancer- and metastasis-initiating cells. J Cell Mol Med. 2013;17:30–54.CrossRefGoogle Scholar
  20. 20.
    Yang-An W, Stevens PD, Gasser ML, Romina A, Tianyan G. Downregulation of PHLPP expression contributes to hypoxia-induced resistance to chemotherapy in colon cancer cells. Mol Cell Biol. 2013;33:4594–605.CrossRefGoogle Scholar
  21. 21.
    Luana S, Sergio R, Marco T, Huafeng Z, Carmen Chak-Lui W, Andrea R, et al. Hypoxia-inducible factor 1-dependent expression of platelet-derived growth factor B promotes lymphatic metastasis of hypoxic breast cancer cells. Proc Natl Acad Sci U S A. 2012;109:E2707–16.CrossRefGoogle Scholar
  22. 22.
    Wang S, Zhou Y, Andreyev O, Hoyt Jr RF, Singh A, Hunt T, et al. Overexpression of FABP3 inhibits human bone marrow derived mesenchymal stem cell proliferation but enhances their survival in hypoxia. Exp Cell Res. 2014;323:56–65.PubMedCrossRefGoogle Scholar
  23. 23.
    Zhang W, Liu Y, Wang CW. S100A4 promotes squamous cell laryngeal cancer Hep-2 cell invasion via NF-kB/MMP-9 signal. Eur Rev Med Pharmacol Sci. 2014;18:1361–7.PubMedGoogle Scholar
  24. 24.
    Bettum IJ, Vasiliauskaite K, Nygaard V, Clancy T, Pettersen SJ, Tenstad E, et al. Metastasis-associated protein S100A4 induces a network of inflammatory cytokines that activate stromal cells to acquire pro-tumorigenic properties. Cancer Lett. 2014;344:28–39.PubMedCrossRefGoogle Scholar
  25. 25.
    Zhang HY, Zheng XZ, Wang XH, Xuan XY, Wang F, Li SS. S100A4 mediated cell invasion and metastasis of esophageal squamous cell carcinoma via the regulation of MMP-2 and E-cadherin activity. Mol Biol Rep. 2012;39:199–208.PubMedCrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Xiaoyan Xuan
    • 1
  • Qianru Li
    • 1
  • Zhongning Zhang
    • 2
  • Ying Du
    • 1
  • Pingping Liu
    • 1
  1. 1.Department of Microbiology and ImmunologyZhengzhou UniversityZhengzhouChina
  2. 2.The Second Affiliated Hospital of Zhengzhou UniversityZhengzhouChina

Personalised recommendations