Expression of RECK and MMPs in Hepatoblastoma and Neuroblastoma and Comparative Analysis on the Tumor Metastasis

  • Xu, Meng (Department of Pediatric Surgery, Linyi Yishui Central Hospital) ;
  • Wang, Hai-Feng (Department of Pediatric Surgery, Linyi Yishui Central Hospital) ;
  • Zhang, Huan-Zhi (Department of Neurosurgery, Anqiu People's Hospital)
  • Published : 2015.05.18


Objective: To explore the expression of RECK and relevant matrix metalloproteinases (MMPs) in hepatoblastoma (HB) and neuroblastoma (NB) and their clinical significance in the tumor metastasis. Materials and Methods: Forty-five wax-stone samples of HB and 43 wax-stone samples of NB removed by surgical resection and confirmed by pathology in Linyi Yishui Central Hospital were selected. According to presence and absence of metastasis, both NB and HB samples were divided into metastatic group and non-metastatic group, namely NB metastatic group (n=28), NB non-metastatic group (n=15), HB metastatic group (n=15) and HB non-metastatic group (n=30). The expression of RECK, membrane type-1 matrix metalloproteinase (MT1-MMP) in HB tissue and RECK, MMP-14 in NB tissue was detected using immunohistochemical method, and the correlation between RECK and MT1-MMP, MMP-14 was analyzed. Results: The metastatic rate of NB was dramatically higher than that of HB, with statistical significance (P=0.003). The positive rate of RECK expression in NB group (30.2%) was slightly lower than in HB group (40.0%), but no significant difference was presented (P=0.338). The positive rate of MMPs expression in NB metastatic group was evidently higher than in HB metastatic group (P=0.024). The results of Spearman correlation analysis revealed that the expression of RECK in HB and NB tissues had a significantly-negative correlation with MT1-MMP and MMP-14, respectively (r=-0.499, P=0.012; r=-0.636, P=0.000). Conclusions: In HB and NB tissues, RECK is expressed lowly, while relevant MMPs highly, and RECK inhibits the tumor invasion and metastasis through negative regulation of relevant MMPs.


Hepatoblastoma;neuroblastoma;RECK;matrix metalloproteinase;metastasis


  1. Alexius-Lindgren M, Andersson E, Lindstedt I, et al (2014). The RECK gene and biological malignancy--its significance in angiogenesis and inhibition of matrix metalloproteinases. Anticancer Res, 34, 3867-73.
  2. Cho YB, Lee WY, Song SY, et al (2007). Matrix metalloproteinase-9 activity is associated with poor prognosis in T3-T4 node-negative colorectal cancer. Hum Pathol, 38, 1603-10.
  3. Clark JC, Thomas DM, Choong PF, et al (2007). RECK--a newly discovered inhibitor of metastasis with prognostic significance in multiple forms of cancer. Cancer Metastasis Rev, 26, 675-83.
  4. Furumoto K, Arii S, Mori A, et al (2001). RECK gene expression in hepatocellular carcinoma: correlation with invasion-related clinicopathological factors and its clinical significance. Reverse-inducing--cysteine-rich protein with Kazal motifs. Hepatology, 33, 189-95.
  5. Jeon HW, Lee YM (2010). Inhibition of histone deacetylase attenuates hypoxia-induced migration andinvasion of cancer cells via the restoration of RECK expression. Mol Cancer Ther, 9, 1361-70.
  6. Khaderi S, Guiteau J, Cotton RT, et al (2014). Role of liver transplantation in the management of hepatoblastoma in the pediatric population. World J Transplant, 4, 294-8.
  7. Kimura T, Okada A, Yatabe T, et al (2010). RECK is up-regulated and involved in chondrocyte cloning in humanosteoarthritic cartilage. Am J Pathol, 176, 2858-67.
  8. Kremer N, Walther AE, Tiao GM (2014). Management of hepatoblastoma: an update. Curr Opin Pediatr, 26, 362-9.
  9. Martinez-Criado Y, Cabello R, Fernandez-Pineda I, et al (2013). Study of the expression of neural stem cell markers in neuroblastoma tumor samples and correlation with prognostic factors. Cir Pediatr, 26, 112-8.
  10. Morandi F, Corrias MV, Pistoia V (2015). Evaluation of bone marrow as a metastatic site of human neuroblastoma. Ann N Y Acad Sci, 1335, 23-31.
  11. Peters H, Augusto TM, Bruni-Cardoso A, et al (2010). RECK expression in the rat ventral prostate: response to castration involves a balance between epithelial and stromal expression. Anat Rec (Hoboken), 293, 993-7.
  12. Verma S, Kesh K, Ganguly N, et al (2014). Matrix metalloproteinases and gastrointestinal cancers: Impacts of dietary antioxidants. World J Biol Chem, 5, 355-76.
  13. Wang JL, Wu DW, Cheng ZZ, et al (2014). Expression of high mobility group box - B1 (HMGB-1) and matrix metalloproteinase-9 (MMP-9) in non-small cell lung cancer (NSCLC). Asian Pac J Cancer Prev, 15, 4865-9.
  14. Xie J, Tan ZH, Tang X, et al (2014). MiR-374b-5p suppresses RECK expression and promotes gastric cancer cell invasion and metastasis. World J Gastroenterol, 20, 17439-47.
  15. Yanez Y, Grau E, Rodriguez-Cortez VC, et al (2015). Two independent epigenetic biomarkers predict survival in neuroblastoma. Clin Epigenetics, 7, 16.
  16. Yang L, Li N, Wang S, et al (2014). Lack of association between the matrix metalloproteinase-2 -1306C>T polymorphism and breast cancer susceptibility: a meta-analysis. Asian Pac J Cancer Prev, 15, 4823-7.
  17. Zhang Y, Zhang WL, Huang DS, et al (2013). Clinical efficacy and prognosis factors for advanced hepatoblastoma in children: a 6-year retrospective study. Asian Pac J Cancer Prev, 14, 4583-9.

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