Expressions of Wnt5a, MMP2, and MMP14 in Gastric Cancer and Their Influences on Clinicopathologic Features_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

JIANG Zhouhua ¹ , WU Shenghua ¹ , LI Xiaoqiang ² , YU Jiwei ¹ , JIANG Bojian ¹

1.Department of General Surgery, No.3 People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 201900, China;;
2.Department of Pathology, No.3 People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai 201900, ChinaCorresponding Author: JIANG Bo-jian, E-mail: jiang_md@hotmail.com;

Corresponding author：

Keywords：

Gastric cancer; Invasion; Metastasis; Epithelial mesenchymal transition; Wnt5a; Matrix metalloproteinase 2; Matrix metalloproteinase 14/MT1-MMP

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Abstract Full text Figures/Tables Video References Cited by

Objective 　To study the expressions of Wnt5a, MMP2, and MMP14 in the primary lesions of gastric cancer and the influences on clinicopathologic features.
Methods 　The expressions of Wnt5a, MMP2, and MMP14 in the specimens of 106 patients with gastric cancer and 39 patients from the adjacent normal gastric tissues were detected by immunohistochemical staining, χ2 test and non-parametric test were used to analyze the relationships among them and between them and their influences on the clinicopathologic features.
Results 　Extensive expressions of Wnt5a, MMP2, and MMP14 were demonstrated in the gastric cancer, which were significantly higher than those in the normal gastric tissues respectively (P lt;0.05). Positive expression of Wnt5a was associated with larger tumor diameter, deeper depth of invasion, higher degree of regional lymph node metastasis, later TNM stage, and higher rate of lymph node metastasis (P lt;0.05). In addition, Wnt5a expression was also associated with lymphatic infiltration and vascular infiltration (P lt;0.05). The expressions of MMP2 and MMP14 were associated with lymphatic infiltration, but not with vascular infiltration. Higher expressions of MMP2 and MMP14 were correlated with deeper tumor invasion, higher degree of regional lymph node metastasis, later TNM stage, and higher rate of lymph node metastasis (P lt;0.05). In addition, higher expression of MMP2 possesed greater tumor diameter (P lt;0.05). Spearman rank correlation analysis revealed the positive relation between Wnt5a and MMP2 　（rs=0.240, P=0.014）, Wnt5a and MMP14 （rs=0.251, P=0.010）, as well as MMP2 and MMP14 （rs=0.444, P=0.000）.
Conclusion 　Higher expressions of Wnt5a, MMP2, and MMP14 seem to promote invasion and metastasis of gastric cancer, and there are positive relations among their expressions.

Citation： JIANG Zhouhua,WU Shenghua,LI Xiaoqiang,YU Jiwei,JIANG Bojian. Expressions of Wnt5a, MMP2, and MMP14 in Gastric Cancer and Their Influences on Clinicopathologic Features. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2010, 17(10): 1077-1082. doi: Copy

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15.	Kurayoshi M, Oue N, Yamamoto H, et al. Expression of Wnt-5a is correlated with aggressiveness of gastric cancer by stimulating cell migration and invasion [J]. Cancer Res, 2006; 66(21): 10439-10448.
16.	江州华, 俞继卫, 姜波健. 基质金属蛋白酶对胃癌微环境调控作用的研究进展 [J]. 中国普外基础与临床杂志, 2009; 16(9): 768-772.
17.	王鹏, 郭琳, 王强. PTEN、Fas/FasL和MMP-2在胃癌组织的表达及其临床意义 [J]. 中国普外基础与临床杂志, 2009; 12(16): 991-995.
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19.	Zheng H, Takahashi H, Murai Y, et al. Expressions of MMP-2, MMP-9 and VEGF are closely linked to growth, invasion, metastasis and angiogenesis of gastric carcinoma [J]. Anticancer Res, 2006; 26(5A): 3579-3583.
20.	Shim KN, Jung SA, Joo YH, et al. Clinical significance of tissue levels of matrix metalloproteinases and tissue inhibitors of metalloproteinases in gastric cancer [J]. J Gastroenterol, 2007; 42(2): 120-128.
21.	Orlichenko LS, Radisky DC. Matrix metalloproteinases stimulate epithelial-mesenchymal transition during tumor development [J]. Clin Exp Metastasis, 2008; 25(6): 593-600.
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23.	Cao J, Chiarelli C, Richman O, et al. Membrane type 1 matrix metalloproteinase induces epithelial-to-mesenchymal transition in prostate cancer [J]. J Biol Chem, 2008; 283(10): 6232-6240.

1. 　吴春晓，郑莹，鲍萍萍, 等. 上海市胃癌发病流行现况与时间趋势分析 [J]. 外科理论与实践, 2008; 13(1): 24-29.
2. 　Wu Y, Zhou BP. New insights of epithelial-mesenchymal transition in cancer metastasis [J]. Acta Biochim Biophys Sin (Shanghai), 2008; 40(7): 643-650.
3. 　Yu JW, Wu JG, Zheng LH, et al. Influencing factors and clinical significance of the metastatic lymph nodes ratio in gastric adenocarcinoma [J]. J Exp Clin Cancer Res, 2009; 28: 55.
4. 　Yu JW, Wu JG, Jiang BJ, et al. Study on lymph node metastasis correlated to lymphangiogenesis, lymphatic vessel invasion and lymph node micrometastasis in gastric cancer [J]. J Surg Res, 2009; 11.doi:10.1016/j.jss.2009.10.030.
5. 　Wodarz A, Nusse R. Mechanisms of Wnt signaling in development [J]. Annu Rev Cell Dev Biol, 1998; 14: 59-88.
6. 　Lustig B, Behrens J. The Wnt signaling pathway and its role in tumor development [J]. Cancer Res Clin Oncol, 2003; 129(4): 199-221.
7. 　刘臻, 崔东旭, 刘宝林, 等. β-连环素基因在乳腺增生及癌组织中表达和突变的研究 [J]. 中国普外基础与临床杂志, 2007; 11(14): 685-688.
8. 　Topol L, Jiang X, Choi H, et al. Wnt-5a inhibits the canonical Wnt pathway by promoting GSK-3-independent β-catenin degradation [J]. J Cell Biol, 2003; 162(5): 899-908.
9. 　Mikels AJ, Nusse R. Purified Wnt5a protein activatesor inhibits β-catenin-TCF signaling depending on receptor context [J]. PLoS Biol, 2006; 4(4): 570-582.
10. 　Kremenevskaja N, von Wasielewski R, Rao AS, et al. Wnt-5a has tumor suppressor activity in thyroid carcinoma [J]. Oncogene, 2005; 24(13): 2144-2154.
11. 　Liu XH, Pan MH, Lu ZF, et al. Expression of Wnt-5a and its clinicopathological significance in hepatocellular carcinoma [J]. Dig Liver Dis, 2008; 40(7): 560-567.
12. 　Da Forno PD, Pringle JH, Hutchinson P, et al. WNT5A expression increases during melanoma progression and correlates with outcome [J]. Clin Cancer Res, 2008; 14(18): 5825-5832.
13. 　Wang Q, Williamson M, Bott S, et al. Hypomethylation of WNT5A, CRIP1 and S100P in prostate cancer [J]. Oncogene, 2007; 26(45): 6560-6565.
14. 　Fernandez-Cobo M, Zammarchi F, Mandeli J, et al. Expression of Wnt5A and Wnt10B in non-immortalized breast cancer cells [J]. Oncol Rep, 2007; 17(4): 903-907.
15. 　Kurayoshi M, Oue N, Yamamoto H, et al. Expression of Wnt-5a is correlated with aggressiveness of gastric cancer by stimulating cell migration and invasion [J]. Cancer Res, 2006; 66(21): 10439-10448.
16. 　江州华, 俞继卫, 姜波健. 基质金属蛋白酶对胃癌微环境调控作用的研究进展 [J]. 中国普外基础与临床杂志, 2009; 16(9): 768-772.
17. 　王鹏, 郭琳, 王强. PTEN、Fas/FasL和MMP-2在胃癌组织的表达及其临床意义 [J]. 中国普外基础与临床杂志, 2009; 12(16): 991-995.
18. 　Koyama S. Enhanced Cell surface expression of matrix metalloproteinases and their inhibitors and tumor-induced host response in progression of human gastric cancer [J]. Dig Dis Sci, 2004; 49(10): 1621-1630.
19. 　Zheng H, Takahashi H, Murai Y, et al. Expressions of MMP-2, MMP-9 and VEGF are closely linked to growth, invasion, metastasis and angiogenesis of gastric carcinoma [J]. Anticancer Res, 2006; 26(5A): 3579-3583.
20. 　Shim KN, Jung SA, Joo YH, et al. Clinical significance of tissue levels of matrix metalloproteinases and tissue inhibitors of metalloproteinases in gastric cancer [J]. J Gastroenterol, 2007; 42(2): 120-128.
21. 　Orlichenko LS, Radisky DC. Matrix metalloproteinases stimulate epithelial-mesenchymal transition during tumor development [J]. Clin Exp Metastasis, 2008; 25(6): 593-600.
22. 　Coyle RC, Latimer A, Jessen JR. Membrane-type 1 matrix metalloproteinase regulates cell migration during zebrafish gastrulation: evidence for an interaction with non-canonical Wnt signaling [J]. Exp Cell Res, 2008; 314(10): 2150-2162.
23. 　Cao J, Chiarelli C, Richman O, et al. Membrane type 1 matrix metalloproteinase induces epithelial-to-mesenchymal transition in prostate cancer [J]. J Biol Chem, 2008; 283(10): 6232-6240.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Expressions of Wnt5a, MMP2, and MMP14 in Gastric Cancer and Their Influences on Clinicopathologic Features

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