JOURNAL OF SHANDONG UNIVERSITY (HEALTH SCIENCES) ›› 2016, Vol. 54 ›› Issue (7): 11-17.doi: 10.6040/j.issn.1671-7554.0.2016.132

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Role of human TIMP-2 protein in the migration and invasion of hepatocellular carcinoma cell

WANG Wei1, CAO Yushan1, SUN Daquan2, HUANG Xiaoqiong1, XU Guoqiang1   

  1. 1. Department of Physiology;
    2. Department of Biochemistry &
    Molecular Biology, Guizhou Medical University, Guiyang 550004, Guizhou, China
  • Received:2016-02-08 Online:2016-07-10 Published:2016-07-10

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Abstract: Objective To collect protein of human TIMP-2 through prokaryotic expression in vitro, and to explore its role in the migration and invasion of hepatocellular carcinoma(HCC)cell. Methods Total RNA was extracted from human hepatoma cell line SMMC-7721, and TIMP-2 cDNA was obtained with RT-PCR. The prokaryotic expression vector pGEX-TIMP-2 was constructed, and then transformed into Origami(DE3). The expressional product was purified with affinity chromatography and identified with Western blotting. The role of TIMP-2 in migration and invasion of HCC cells were detected with RNAi technology and adding extraneous TIMP-2 protein. The mRNA and protein expressions of endogenous TIMP-2 in HCC cells were detected with real-time fluorescence quantitative PCR and Western blotting after transfection with siTIMP-2. Results Adding of exogenous TIMP-2 suppressed the migration and invasion of HCC; knock-down of TIMP-2 enhanced the migration and invasion of HCC; conditioned medium of hepatic stellate cells promoted the migration and invasion of HCC, which could be inhibited by TIMP-2 protein. Conclusion The level of TIMP-2 protein in the microenvironment is closely related to the migration and invasion of HCC.

Key words: Tissue inhibitor of matrix metalloproteinases-2, Invasion, Hepatocellular carcinoma, Migration

CLC Number: 

  • R735.7
[1] Morise Z, Kawabe N, Tomishige H, et al. Recent advances in liver resection for hepatocellular carcinoma[J]. Front Surg, 2014, 1: 21. doi: 10.3389/fsurg.2014.00021.
[2] Giannelli G, Rani B, Dituri F, et al. Moving towards personalised therapy in patients with hepatocellular carcinoma: the role of the microenvironment[J]. Gut, 2014, 63(10): 1668-1676.
[3] Cirri P, Chiarugi P. Cancer-associated-fibroblasts and tumor cells: a diabolic liaison driving cancer progression[J]. Cancer Metastasis Rev, 2012, 31(1-2): 195-208.
[4] Amann T, Bataille F, Spruss T, et al. Activated hepatic stellate cellss promote tumorigenicity of hepatocellular carcinoma[J]. Cancer Sci, 2009, 100(4): 646-653.
[5] Yang SF, Chen MK, Hsieh YS, et al. Antimetastatic effects of Terminalia catappa L. on oral cancer via a down-regulation of metastasis-associated proteases[J]. Food Chem Toxicol, 2010, 48(4): 1052-1058.
[6] Yeh CB, Hsieh MJ, Hsieh YH, et al. Antimetastatic effects of norcantharidin on hepatocellular carcinoma by transcriptional inhibition of MMP-9 through modulation of NF-kB activity[J]. PLoS One, 2012, 7(2): e31055. doi: 10.1371/journal.pone.0031055.
[7] Breitkreutz D, Koxholt I, Thiemann K, et al. Skin basement membrane: the foundation of epidermal integrity-BM functions and diverse roles of bridging molecules nidogen and perlecan[J]. Biomed Res Int, 2013, 2013: 179784. doi:10.1155/2013/179784.
[8] Stetler-Stevenson WG, Gavil NV. Normalization of the tumor microenvironment: evidence for tissue inhibitor of metalloproteinase-2 as a cancer therapeutic[J]. Connect Tissue Res, 2014, 55(1): 13-19.
[9] Shao J, Xu Z, Peng X, et al. Gefitinib synergizes with irinotecan to suppress hepatocellular carcinoma via antagonizing rad51-mediated DNA-repair[J]. PLoS One, 2016, 11(11): e0146968. doi: 10.1371/journal.pone.0146968.
[10] Johansson E, Komuro A, Iwata C, et al. Exogenous introduction of tissue inhibitor of metalloproteinase 2 reduces accelerated growth of TGF-beta-disrupted diffuse-type gastric carcinoma[J]. Cancer Sci, 2010, 101(11): 2398-2403.
[11] Mendes O, Kim HT, Lungu G. et al. MMP2 role in breast cancer brain metastasis development and its regulation by TIMP2 and ERK1/2[J]. Clin Exp Metastasis, 2007, 24(5): 341-351.
[12] Liang B, Yin JJ, Zhan XR. MiR-301a promotes cell proliferation by directly targeting TIMP-2 in multiple myeloma[J]. Int J Clin Exp Pathol, 2015, 8(8): 9168-9174.
[13] Dai Y, Xia W, Song T, et al. MicroRNA-200b is overexpressed in endometrial adenocarcinomas and enhances MMP2 activity by downregulating TIMP-2 in human endometrial cancer cell line HEC-1A cells[J]. Nucleic Acid Ther, 2013, 23(1): 29-34.
[14] Zhu M, Zhang N, Zhao L, et al. MicroRNA-106a targets TIMP-2 to regulate invasion and metastasis of gastric cancer[J]. FEBS Lett, 2014, 588(4): 600-607.
[15] Lu GJ, Dong YQ, Jiao LY, et al. MiRNA-221 promotes proliferation, migration and invasion by targeting TIMP-2 in renal cell carcinoma[J]. Int J Clin Exp Pathol, 2015, 8(5): 5224-5229.
[16] Braicu EI, Gasimli K, Richter R, et al. Role of serum VEGFA, TIMP-2, MMP2 and MMP9 in monitoring response to adjuvant radiochemotherapy in patients with primary cervical cancer-results of a companion protocol of the randomized NOGGO-AGO phase III clinical trial[J]. Anticancer Res, 2014, 34(1): 385-391.
[17] Chen TY, Li YC, Liu YF, et al. Role of MMP14 gene polymorphisms in susceptibility and pathological development to hepatocellular carcinoma[J]. Ann Surg Oncol, 2011, 18(8): 2348-2356.
[18] Bourboulia D, Han H, Stetler-Stevenson WG, et al. TIMP-2 modulates cancer cell transcriptional profile and enhances E-cadherin/beta-catenin complex expression in A549 lung cancer cells[J]. Oncotarget, 2013, 4(1): 163-173.
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