The Research Progress of Matrix Metalloproteinases in Invasion and Metastasis of Gastric Cancer
DOI: 10.12677/WJCR.2015.52004, PDF, HTML, XML, 下载: 2,581  浏览: 10,963 
作者: 熊亚立, 向 征:重庆医科大学第一附属医院,重庆
关键词: 胃癌侵袭和转移基质金属蛋白酶Cancer of the Stomach Invasion and Metastasis Matrix Metalloproteinases
摘要: 侵袭和转移是胃癌最主要的生物学特征,也是导致治疗失败和患者死亡的主要原因,因此阻止胃癌的侵袭和转移在治疗过程中具有非常重要的意义。胃癌发生侵袭和转移,必须伴随细胞外基质和基底膜完整性的破坏、肿瘤细胞粘附能力的改变、血管生成,基质金属蛋白酶(matrix metalloproteinases, MMPs)则在其中扮演着重要的角色,目前以其作为治疗靶点的药物已进入临床试验阶段。本文就MMPs在胃癌侵袭和转移中的作用做一简单综述。
Abstract: As is known to all, the most important thing for treating gastric cancer is to prevent its invasion and metastasis, which are the most common causes of treatment failure and mortality. When invasion and metastasis happened, it always accompanied with the integrity destruction of the extracellular matrix and the basement membrane. And it often leads to the change of tumor cell adhesion ability and angiogenesis as well. Matrix metalloproteinases (MMPs) plays a significant role in the invasion and metastasis of gastric cancer. As a therapeutic target, the drugs affected on MMPs had reached the stage of clinical trials. I will make a simple review to introduce the role of MMPs in the invasion and metastasis of gastric cancer.
文章引用:熊亚立, 向征. 基质金属蛋白酶与胃癌侵袭和转移的研究进展[J]. 世界肿瘤研究, 2015, 5(2): 21-26. http://dx.doi.org/10.12677/WJCR.2015.52004


[1] Sampieri, C.L., León-Córdoba, K. and Remes-Troche, J.M. (2013) Matrix metalloproteinases and their tissue inhibitors in gastric cancer as molecular markers. Journal of Cancer Research and Therapeutics, 9, 356-363.
[2] Zhang, M., Zhu, G.Y., Gao, H.Y., et al. (2011) Expression of tissue levels of matrix metalloproteinases and tissue inhibitors of metalloproteinases in gastric adenocarcinoma. Journal of Surgical Oncology, 103, 243-247.
[3] Jiao, F., Jin, Z., Wang, L. and Wang, L. (2013) Research and clinical applications of molecular biomarkers in gastrointestinal carcinoma. Biomed Reports, 1, 819-827.
[4] Gencer, S., Cebeci, A. and Irmak-Yazicioglu, M.B. (2013) Matrix metalloproteinase gene expressions might be oxidative stress targets in gastric cancer cell lines. Chinese Journal of Cancer Research, 25, 322-333.
[5] Hashimoto, H., Takeuchi, T., Komatsu, K., et al. (2011) Structural basis for matrix metalloproteinase-2 (MMP-2)-se- lective inhibitory action of β-amyloid precursor protein-derived inhibitor. The Journal of Biological Chemistry, 286, 33236-33243.
[6] Visse, R. and Nagase, H. (2003) Matrix metalloproteinases and tissue inhibitors of metalloproteinases: Structure, function, and biochemistry. Circulation Research, 92, 827-839.
[7] Maradni, A., Khoshnevisan, A., Mousavi, S.H., et al. (2013) Role of matrix metalloproteinases (MMPs) and MMP inhibitors on intracranial aneurysms: A review article. Medical Journal of the Islamic Republic of Iran, 27, 249-254.
[8] Al-Batran, S.E., Pauligk, C., Wirtz, R., et al. (2012) The validation of matrix metalloproteinase-9 mRNA gene expression as a predictor of outcome in patients with metastatic gastric cancer. Annals of Oncology, 23, 1699-1705.
[9] Deryugina, E.I. and Quigley, J.P. (2010) Pleiotropic roles of matrix metalloproteinases in tumor angiogenesis: Contrasting, overlapping and compensatory functions. Biochimica et Biophysica Acta, 1803, 103-120.
[10] Kang, M.H., Oh, S.C., Lee, H.J., et al. (2011) Metastatic function of BMP-2 in gastric cancer cells: The role of PI3K/ AKT, MAPK, the NF-κB pathway, and MMP-9 expression. Experimental Cell Research, 317, 1746-1762.
[11] Jin, X., Zhu, Z. and Shi, Y. (2014) Metastasis mechanism and gene/protein expression in gastric cancer with distant organs metastasis. Bulletin du Cancer, 101, 1-12.
[12] Amălinei, C., Căruntu, I.D., Giuşcă, S.E. and Bălan, R.A. (2010) Matrix metalloproteinases involvement in pathologic conditions. Romanian Journal of Morphology and Embryology, 51, 215-228.
[13] Sillat, T., Saat, R., Pöllänen, R., Hukkanen, M., Takagi, M. and Konttinen, Y.T. (2012) Basement membrane collagen type IV expression by human mesenchymal stem cells during adipogenic differentiation. Journal of Cellular and Molecular Medicine, 16, 1485-1495.
[14] Mroczko, B., Lukaszewicz-Zając, M., Gryko, M., Kędra, B. and Szmitkowski, M. (2011) Clinical significance of serum levels of matrix metalloproteinase 2 (MMP-2) and its tissue inhibitor (TIMP-2) in gastric cancer. Folia Histochemica et Cytobiologica, 49, 125-131.
[15] Liotta, L.A., Tryggvason, K., Garbisa, S., Hart, I., Foltz, C.M. and Shafie, S. (1980) Metastatic potential correlates with enzymatic degradation of basement membrane collagen. Nature, 284, 67-68.
[16] Ferretti, G., Fabi, A., Carlini, P., Papaldo, P., Cordiali Fei, P., Di Cosimo, S., et al. (2005) Zoledronic-acid-induced circulating level modifications of angiogenic factors, metalloproteinases and proinflammatory cytokines in metastatic breast cancer patients. Oncology, 69, 35-43.
[17] Gerstein, E.S., Sini, L., Ryabov, A.B., Dvorova, E.K., Yurchenko, A.A., Stilidi, I.S., et al. (2009) Comparative enzyme immunoassay of matrix metalloproteinases-2, -7, -9 and their tissue inhibitor-2 in tumors and plasma of patients with gastric cancer. Bulletin of Experimental Biology and Medicine, 148, 899-902.
[18] Nisato, R.E., Hosseini, G., Sirrenberg, C., Butler, G.S., Crabbe, T., Docherty, A.J.P., et al. (2005) Dissecting the role of matrix metalloproteinases (MMPs) and integrin αvβ3 in angiogenesis in vitro: Absence of hemopex in C domain bioactivity, but membrane-type1-MMP and αvβ3 are critical. Cancer Research, 65, 9377-9387.
[19] Shih, Y.W., Chien, S.T., Chen, P.S., Lee, J.H., Wu, S.H. and Yin, L.T. (2010) α-mangostin suppresses phorbol 12-myristate 13-acetate-induced MMP-2/MMP-9 expressions via αvβ3 integrin/FAK/ERK and NF-κB signaling pathway in human lung adenocarcinoma A549 cells. Cell Biochemistry and Biophysics, 58, 31-44.
[20] Temma, T., Sano, K., Kuge, Y., Kamihashi, J., Takai, N., Ogawa, Y. and Saji, H. (2009) Development of a radiolabeled probe for detecting membrane type-1 matrix metalloproteinase on malignant trumors. Biological and Pharmaceutical Bulletin, 32, 1272-277.
[21] Perng, D.W., Chang, K.T., Su, K.C., Wu, Y.C., Chen, C.S., Hsu, W.H., et al. (2011) Matrix metalloprotease-9 induces transforming growth factor-β(1) production in airway epithelium via activation of epidermal growth factor receptors. Life Sciences, 89, 204-212.
[22] Siqueira, A.S., Carvalho, M.R., Monteiro, A.C., Freitas, V.M., Jaeger, R.G. and Pinheiro, J.J.V. (2010) Matrix metalloproteinases, TIMPs and growth factors regulating ameloblastoma behavior. Histopathology, 57, 128-137.
[23] Saito, Y., Sekine, W., Sano, R., Komatsu, S., Mizuno, H., Katabami, K., et al. (2010) Potentiation of cell invasion and matrix metalloproteinase production by α3β1 integrin-mediated adhesion of gastric carcinoma cells to laminin-5. Clinical & Experimental Metastasis, 27, 197-205.
[24] Jang, K.J., Son, I.S., Shin, D.Y., Yoon, H.M. and Choi, Y.H. (2011) Anti-invasive activity of ethanol extracts of Ganoderma lucidum through tightening of tight junctions and inhibition of matrix metalloproteinase activities in human gastric carcinoma cells. Journal of Acupuncture and Meridian Studies, 4, 225-235.
[25] Shim, K.N., Jung, S.A., Joo, Y.H. and Yoo, K. (2007) Clinical significance of tissue levels of matrix metalloproteinases and tissue inhibitors of metalloproteinases in gastric cancer. Journal of Gastroenterology, 42, 120-128.
[26] Partyka, R., Gonciarz, M., Jałowiecki, P., Kokocińska, D. and Byrczek, T. (2012) VEGF and metalloproteinase 2 (MMP 2) expression in gastric cancer tissue. Medical Science Monitor, 18, 130-134.
[27] Koskensalo, S., Mrena, J., Wiksten, J.P., Nordling, S., Kokkola, A., Hagström, J. and Haglund, C. (2010) MMP-7 overexpression is an independent prognostic marker in gastric cancer. Tumor Biology, 31, 149-155.
[28] Lenger, J., Kaschani, F., Lenz, T., Dalhoff, C., Villamor, J.G., Köster, H., et al. (2012) Labeling and enrichment of Arabidopsis thaliana matrix metalloproteases using an active-site directed, marimastat-based photoreactive probe. Bioorganic & Medicinal Chemistry, 20, 592-596.
[29] van Wijngaarden, J., Snoeks, T.J., van Beek, E., Bloys, H., Kaijzel, E.L., et al. (2010) An in vitro model that can distinguish between effects on angiogenesis and on established vasculature: Actions of TNP-470, marimastat and the tubulin-binding agent Ang-510. Biochemical and Biophysical Research Communications, 391, 1161-1165.
[30] 骆殊, 沈洪, 朱学军, 刘丽, 李春婷, 刘亚军 (2009) 黄芪、莪术配伍对胃癌MKN-45细胞COX-1, COX-2 , NF-κB, VEGF, MMP-2表达的影响. 现代中西医结合杂志, 4, 351-353.
[31] 胡晓慧, 沈飞, 董宁征, 李佩霞, 阮长耿 (2005) 抗人基质金属蛋白酶-2的单抗制备及功能研究. 中国病理生理杂志, 5, 876-881.