Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
권호 표지
DOI QR코드

DOI QR Code

S100A4 Expression is Closely Linked to Genesis and Progression of Glioma by Regulating Proliferation, Apoptosis, Migration and Invasion

  • Jin, Ting (Department of Neurosurgery, The First Affiliated Hospital of Liaoning Medical University) ;
  • Zhang, Zhuo (Department of Stomatology, The First Affiliated Hospital of Liaoning Medical University) ;
  • Yang, Xue-Feng (The Key Laboratory of Brain and Spinal Injury of Liaoning Province, The First Affiliated Hospital of Liaoning Medical University) ;
  • Luo, Jun-Sheng (The Key Laboratory of Brain and Spinal Injury of Liaoning Province, The First Affiliated Hospital of Liaoning Medical University)
  • Published : 2015.04.14
Download PDF
⟨ Previous Next ⟩

Abstract

Background: The calcium-binding S100A4 protein is involved in epithelial to mesenchymal transition, oncogenic transformation, angiogenesis, cytoskeletal integrity, mobility and metastasis of cancer cells. This study aimed to clarify the roles of S100A4 in genesis and progression of glioma. Materials and Methods: S100A4 expression was examined by real-time RT-CPR and Western blot in glioma and paired normal brain tissue (n=69), and compared with clinicopathological parameters of tumors. In addition, glioma U251 cells transfected with an S100A4-expressing plasmid were examined for proliferation by MTT, apoptosis by Annexin V-FITC, and migration and invasion with Transwell chambers. Results: Increased S100A4 mRNA expression was found in gliomas, compared with paired non-tumor tissue (p<0.001). Gradual elevation of overexpression of S100A4 was observed with increasing glioma grade (p<0.001). Astrocytoma showed lower S100A4 mRNA expression than oligodendrogliomas, with glioblastomas having highest values (p<0.001). Similar results were obtained for S100A4 protein, a positive link being found between mRNA and protein expression in gliomas (p<0.001). There was higher growth, lower apoptosis, stronger migration and invasion of S100A4 transfectants than control and mock transfected cells (p<0.001). Conclusions: These findings indicate that up-regulated S100A4 expression is positively linked to pathogenesis, progression and histogenesis of glioma by modulating proliferation, apoptosis, migration and invasion.

Keywords

References

  1. Belot N, Pochet R, Heizmann CW, Kiss R, Decaestecker C (2002). Extracellular S100A4 stimulates the migration rate of astrocytic tumor cells by modifying the rganization of their actin cytoskeleton. Biochim Biophys Acta, 1600, 74-83. https://doi.org/10.1016/S1570-9639(02)00447-8
  2. Boye K, Maelandsmo GM (2010). S100A4 and metastasis: a small actor playing many roles. Am J Pathol, 176, 528-35. https://doi.org/10.2353/ajpath.2010.090526
  3. Chen D, Zheng XF, Yang ZY, et al (2012). S100A4 silencing blocks invasive ability of esophageal squamous cell carcinoma cells. World J Gastroenterol, 18, 915-22. https://doi.org/10.3748/wjg.v18.i9.915
  4. Dahlmann M, Okhrimenko A, Marcinkowski P, et al (2014). RAGE mediates S100A4-induced cell motility via MAPK/ERK and hypoxia signaling and is a prognostic biomarker for human colorectal cancer metastasis. Oncotarget, 5, 3220-33. https://doi.org/10.18632/oncotarget.1908
  5. Feng LZ, Zheng XY, Zhou LX, et al (2011). Correlation between expression of S100A4 and VEGF-C, and lymph node metastasis and prognosis in gastric carcinoma. J Int Med Res, 39, 1333-43. https://doi.org/10.1177/147323001103900420
  6. Horiuchi A, Hayashi T, Kikuchi,N, et al (2012). Hypoxia upregulates ovarian cancer invasiveness via the binding of HIF-$1{\alpha}$ to a hypoxia-induced, methylation-free hypoxia response element of S100A4 gene. Int J Cancer, 131, 1755-67. https://doi.org/10.1002/ijc.27448
  7. Ismail NI, Kaur G, Hashim H, Hassan MS (2008). S100A4 overexpression proves to be independent marker for breast cancer progression. Cancer Cell Int, 8, 12. https://doi.org/10.1186/1475-2867-8-12
  8. Jenkinson SR, Barraclough R, West CR, Rudland PS (2004). S100A4 regulates cell motility and invasion in an in vitro model for breast cancer metastasis. Br J Cancer, 90, 253-62. https://doi.org/10.1038/sj.bjc.6601483
  9. Jia W, Gao XJ, Zhang ZD, Yang ZX, Zhang G (2013). S100A4 silencing suppresses proliferation, angiogenesis and invasion of thyroid cancer cells through downregulation of MMP-9 and VEGF. Eur Rev Med Pharmacol Sci, 17, 1495-508.
  10. Kang YG, Jung CK, Lee A, Kang WK, Oh ST, Kang CS (2012). Prognostic significance of S100A4 mRNA and protein expression in colorectal cancer. J Surg Oncol, 105, 119-24. https://doi.org/10.1002/jso.22070
  11. Kim JH, Kim CN, Kim SY, et al (2009). Enhanced S100A4 protein expression is clinicopathologically significant to metastatic potential and p53 dysfunction in colorectal cancer. Oncol Rep, 22, 41-7.
  12. Liang J, Piao Y, Holmes L, et al (2014). Neutrophils promote the malignant glioma phenotype through S100A4. Clin Cancer Res, 20, 187-98. https://doi.org/10.1158/1078-0432.CCR-13-1279
  13. Liu J, Guo Y, Fu S, Yang M, Sun KL, Fu WN (2010). Hypomethylation-induced expression of S100A4 increases the invasiveness of laryngeal squamous cell carcinoma. Oncol Rep, 23, 1101-7.
  14. Louis DN, Ohgaki H, Wiestler OD, Cavenee WK (2007). WHO classification of tumors of the central nervous system, Fourth Edition IARC.
  15. Maelandsmo GM, Hovig E, Skrede M, et al (1996). Reversal of the in vivo metastatic phenotype of human tumor cells by an anti-CAPL (mts1) ribozyme. Cancer Res, 56, 5490-8.
  16. Matsumoto K, Irie A, Satoh T, et al (2007). Expression of S100A2 and S100A4 predicts for disease progression and patient survival in bladder cancer. Urology, 70, 602-7. https://doi.org/10.1016/j.urology.2007.04.007
  17. Mishra SK, Siddique HR, Saleem M (2012). S100A4 calcium-binding protein is key player in tumor progression and metastasis: preclinical and clinical evidence. Cancer Metastasis Rev, 31, 163-72. https://doi.org/10.1007/s10555-011-9338-4
  18. Sack U, Walther W, Scudiero D, et al (2011). S100A4-induced cell motility and metastasis is restricted by the Wnt/${\beta}$-catenin pathway inhibitor calcimycin in colon cancer cells. Mol Biol Cell, 22, 3344-54. https://doi.org/10.1091/mbc.E10-09-0739
  19. Schwartzbaum JA, Fisher JL, Aldape KD, Wrensch M (2006). Epidemiology and molecular pathology of glioma. Nat Clin Pract Neurol, 2, 494-503.
  20. Sekine H, Chen N, Sato K, et al (2012). S100A4, frequently overexpressed in various human cancers, accelerates cell motility in pancreatic cancer cells. Biochem Biophys Res Commun, 429, 214-9. https://doi.org/10.1016/j.bbrc.2012.10.048
  21. Simpson PT, Shoker BS, Barraclough R, et al (2003). Examination of tumour histopathology and gene expression in a neu/S100A4 transgenic model of metastatic breast cancer. Int J Exp Pathol, 84, 173-84. https://doi.org/10.1046/j.1365-2613.2003.00350.x
  22. Takenaga K, Nakamura Y, Sakiyama S (1997). 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, 14, 331-7. https://doi.org/10.1038/sj.onc.1200820
  23. Takenaga K, Nygren J, Zelenina M, et al (2007). Modified expression of Mts1/S100A4 protein in C6 glioma cells or surrounding astrocytes affects migration of tumor cells in vitro and in vivo. Neurobiol Dis, 25, 455-63. https://doi.org/10.1016/j.nbd.2006.10.021
  24. Trabelsi S, Brahim DH, Ladib M (2014). Glioma epidemiology in the central Tunisian population: 1993-2012. Asian Pac J Cancer Prev, 15, 8753-7. https://doi.org/10.7314/APJCP.2014.15.20.8753
  25. Tsukamoto N, Egawa S, Akada M, et al (2013). The expression of S100A4 in human pancreatic cancer is associated with invasion. Pancreas, 42, 1027-33. https://doi.org/10.1097/MPA.0b013e31828804e7
  26. Walker DG, Duan W, Kaye AH, Lavin MF (1995). Homozygous deletions of the MTS1 gene are rare in non-astrocytic brain tumors. Biochem Biophys Res Commun, 211, 404-9. https://doi.org/10.1006/bbrc.1995.1828
  27. Wang H, Duan L, Zou Z, et al (2014). Activation of the PI3K/Akt/mTOR/p70S6K pathway is involved in S100A4-induced viability and migration in colorectal cancer cells. Int J Med Sci, 11, 841-9. https://doi.org/10.7150/ijms.8128
  28. Xie R, Schlumbrecht MP, Shipley GL, Xie S, Bassett RL Jr., Broaddus RR (2009). S100A4 mediates endometrial cancer invasion and is a target of TGF-beta1 signaling. Lab Invest, 89, 937-47. https://doi.org/10.1038/labinvest.2009.52
  29. Xu X, Su B, Xie C, et al (2014). Sonic hedgehog-gli1 signaling pathway regulates the epithelial mesenchymal transition (EMT) by mediating a new target gene, S100A4, in pancreatic cancer cells. PLoS One, 9, 96441. https://doi.org/10.1371/journal.pone.0096441
  30. Yang H, Zhao K, Yu Q, Wang X, Song Y, Li R (2012). Evaluation of plasma and tissue S100A4 protein and mRNA levels as potential markers of metastasis and prognosis in clear cell renal cell carcinoma. J Int Med Res, 40, 475-85. https://doi.org/10.1177/147323001204000209
  31. Zhang G, Li M, Jin J, Bai Y, Yang C (2011). Knockdown of S100A4 decreases tumorigenesis and metastasis in osteosarcoma cells by repression of matrix metalloproteinase-9. Asian Pac J Cancer Prev, 12, 2075-80.
  32. Zhang HY, Zheng XZ, Wang XH, Xuan XY, Wang F, Li SS (2012a). S100A4 mediated cell invasion and metastasis of esophageal squamous cell carcinoma via the regulation of MMP-2 and E-cadherin activity. Mol Biol Rep, 39, 199-208. https://doi.org/10.1007/s11033-011-0726-1
  33. Zhang K, Zhang M, Zhao H, Yan B, Zhang D, Liang J (2012). S100A4 regulates motility and invasiveness of human esophageal squamous cell carcinoma through modulating the AKT/Slug signal pathway. Dis Esophagus, 25, 731-9. https://doi.org/10.1111/j.1442-2050.2012.01323.x
  34. Zhao Y, Zhang T, Wang Q (2013). S100 calcium-binding protein A4 is a novel independent prognostic factor for the poor prognosis of gastric carcinomas. Oncol Rep, 30, 111-8.

Cited by

  1. Serum levels of S100A6 are unaltered in patients with resectable cholangiocarcinoma vol.5, pp.1, 2016, https://doi.org/10.1186/s40169-016-0120-7
  2. Antagonistic Effects of Endogenous Nitric Oxide in a Glioblastoma Photodynamic Therapy Model vol.92, pp.6, 2016, https://doi.org/10.1111/php.12636
  3. Voltage-gated calcium channels: Novel targets for cancer therapy vol.14, pp.2, 2017, https://doi.org/10.3892/ol.2017.6457