Expression of Matrilysin in Gastric Cancer and Its Significance: An Indicator for Determining Invasion, Metastasis, and Prognosis_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

HUANG Baojun ¹ , ZHAO Yujie ² , ZHANG Yukui ² , XU Huimian. ¹

1.Department of Surgical Oncology, The First Hospital of China Medical University, Shenyang 110001, Liaoning Province, China;;
2.Center of Biochip, China Medical University, Shenyang 110001, Liaoning Province, China;

Corresponding author：

Keywords：

Gastric cancer; Matrilysin gene; Invasion; Metastasis; Prognosis

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ObjectiveTo study the expression of matrilysin in gastric cancer and to evaluate the correlation between its expression and invasion, metastasis, and prognosis. MethodsA total of 52 patients with gastric cancer were selected and followed up. The expressions of matrilysin in gastric primary focus, normal gastric mucosa, and metastatic lymph nodes were examined by reverse transcriptionpolymerase chain reaction (RT-PCR), Western blot, and immunohistochemistry, respectively. The correlations between matrilysin expression and tumor invasion, metastasis, and prognosis were assessed. ResultsThe expressions of matrilysin in gastric primary focus and metastatic lymph nodes significantly increased, while decreased or loss in normal gastric mucosa (P lt;0.001). The higher concordance was seen between the levels of mRNA and protein (P lt;0.001). Among patients with infiltrating type, penetrated serosa, area of serosa involved more than 20 cm2, and metastatic lymph nodes more than 7, the expression of matrilysin was significantly higher (P lt;0.01). The survival rate of patients with matrilysin higher expression (34.1%) was significantly lower than that with matrilysin lower expression (55.6%), χ2=9.778， P=0.002. Conclusions Up-regulated expression of matrilysin plays an important role in tumor invasion, metastasis, and poor prognosis, and it is a good molecular marker to reflect the biological behaviors of gastric cancer.

Citation： HUANG Baojun,ZHAO Yujie,ZHANG Yukui,XU Huimian.. Expression of Matrilysin in Gastric Cancer and Its Significance: An Indicator for Determining Invasion, Metastasis, and Prognosis. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2011, 18(10): 1063-1068. doi: Copy

1.	Nagase H, Woessner JF Jr. Matrix metalloproteinases [J]. J Biol Chem, 1999, 274(31): 2149121494.
2.	Wroblewski LE, Noble PJ, Pagliocca A, et al. Stimulation of MMP7 (matrilysin) by Helicobacter pylori in human gastric epithelial cells: role in epithelial cell migration [J]. J Cell Sci, 2003, 116(Pt 14): 30173026.
3.	Miyamoto S, Yano K, Sugimoto S, et al. Matrix metalloproteinase7 facilitates insulinlike growth factor bioavailability through its proteinase activity on insulinlike growth factor binding protein 3 [J]. Cancer Res, 2004, 64(2): 665671.
4.	Ajisaka H, Yonemura Y, Miwa K. Correlation of lymph node metastases and expression of matrix metalloproteinase7 in patients with gastric cancer [J]. Hepatogastroenterology, 2004, 51(57): 900905.
5.	Sasaki H, Yukiue H, Moiriyama S, et al. Clinical significance of matrix metalloproteinase7 and Ets1 gene expression in patients with lung cancer [J]. J Surg Res, 2001, 101(2): 242247.
6.	Masaki T, Matsuoka H, Sugiyama M, et al. Matrilysin (MMP7) as a significant determinant of malignant potential of early invasive colorectal carcinomas [J]. Br J Cancer, 2001, 84(10): 13171321.
7.	Yamamoto H, Adachi Y, Itoh F, et al. Association of matrilysin expression with recurrence and poor prognosis in human esophageal squamous cell carcinoma [J]. Cancer Res, 1999, 59(14): 33133316.
8.	Okayama H, Kumamoto K, Saitou K, et al. CD44v6, MMP7 and nuclear Cdx2 are significant biomarkers for prediction of lymph node metastasis in primary gastric cancer [J]. Oncol Rep, 2009, 22(4): 745755.
9.	黄宝俊, 徐惠绵, 赵雨杰. 应用低密度芯片初步筛选胃癌淋巴转移相关基因的研究 [J]. 中华肿瘤防治杂志, 2006, 13(24): 18411845.
10.	黄宝俊, 赵雨杰, 徐惠绵, 等. hRad17 mRNA 在胃癌中表达的意义 [J]. 中华肿瘤杂志, 2003, 25(2): 160162.
11.	Wilson CL, Matrisian LM. Matrilysin: an epithelial matrix metalloproteinase with potentially novel functions [J]. Int J Biochem Cell Biol, 1996, 28(2): 123136.
12.	Nishizuka I, Ichikawa Y, Ishikawa T, et al. Matrilysin stimulates DNA synthesis of cultured vascular endothelial cells and induces angiogenesis in vivo [J]. Cancer Lett, 2001, 173(2): 175182.
13.	Wilson CL, Heppner KJ, Labosky PA, et al. Intestinal tumorigenesis is suppressed in mice lacking the metalloproteinase matrilysin [J]. Proc Natl Acad Sci U S A， 1997, 94(4): 14021407.
14.	Goss KJ, Brown PD, Matrisian LM. Differing effects of endogenous and synthetic inhibitors of metalloproteinases on intestinal tumorigenesis [J]. Int J Cancer, 1998, 78(5): 629635.
15.	Brabletz T, Jung A, Dag S, et al. betacatenin regulates the expression of the matrix metalloproteinase7 in human colorectal cancer [J]. Am J Pathol, 1999, 155(4): 10331038.
16.	Ohnami S, Matsumoto N, Nakano M, et al. Identification of genes showing differential expression in antisense Krastransduced pancreatic cancer cells with suppressed tumorigenicity [J]. Cancer Res, 1999, 59(21): 55655571.
17.	Fukushima H, Yamamoto H, Itoh F, et al. Association of matrilysin mRNA expression with Kras mutations and progression in pancreatic ductal adenocarcinomas [J]. Carcinogenesis, 2001, 22(7): 10491052.
18.	Maruta S, Sakai H, Kanda S, et al. E1AF expression is associated with extraprostatic growth and matrix metalloproteinase7 expression in prostate cancer [J]. APMIS, 2009, 117(11): 791796.
19.	Liu XP, Kawauchi S, Oga A, et al. Prognostic significance of matrix metalloproteinase7 (MMP7) expression at the invasive front in gastric carcinoma [J]. Jpn J Cancer Res, 2002, 93(3): 291295.
20.	Ii M, Yamamoto H, Adachi Y, et al. Role of matrix metalloproteinase7 (matrilysin) in human cancer invasion, apoptosis, growth, and angiogenesis [J]. Exp Biol Med (Maywood), 2006, 231(1): 2027.
21.	Yamashita K, Azumano I, Mai M, et al. Expression and tissue localization of matrix metalloproteinase 7 (matrilysin) in human gastric carcinomas. Implications for vessel invasion and metastasis [J]. Int J Cancer, 1998, 79(2): 187194.
22.	Koskensalo S, Mrena J, Wiksten JP, et al. MMP7 overexpression is an independent prognostic marker in gastric cancer [J]. Tumour Biol, 2010, 31(3): 149155.
23.	Yeh YC, Sheu BS, Cheng HC, et al. Elevated serum matrix metalloproteinase3 and 7 in H. pylorirelated gastric cancer can be biomarkers correlating with a poor survival [J]. Dig Dis Sci, 2010, 55(6): 16491657.
24.	冯众一, 徐惠绵, 黄宝俊. 基质金属蛋白酶7基因表达与胃癌生物学行为及腹膜转移的关系 [J]. 肿瘤学杂志, 2004, 10(6): 413415.
25.	Yoshikawa T, Yanoma S, Tsuburaya A, et al. Expression of MMP7 and MT1MMP in peritoneal dissemination of gastric cancer [J]. Hepatogastroenterolog, 2006, 53(72): 964967.
26.	Yonemura Y, Endo Y, Fujita H, et al. Inhibition of peritoneal dissemination in human gastric cancer by MMP7specific antisense oligonucleotide [J]. J Exp Clin Cancer Res, 2001, 20(2): 205212.

1. Nagase H, Woessner JF Jr. Matrix metalloproteinases [J]. J Biol Chem, 1999, 274(31): 2149121494.
2. Wroblewski LE, Noble PJ, Pagliocca A, et al. Stimulation of MMP7 (matrilysin) by Helicobacter pylori in human gastric epithelial cells: role in epithelial cell migration [J]. J Cell Sci, 2003, 116(Pt 14): 30173026.
3. Miyamoto S, Yano K, Sugimoto S, et al. Matrix metalloproteinase7 facilitates insulinlike growth factor bioavailability through its proteinase activity on insulinlike growth factor binding protein 3 [J]. Cancer Res, 2004, 64(2): 665671.
4. Ajisaka H, Yonemura Y, Miwa K. Correlation of lymph node metastases and expression of matrix metalloproteinase7 in patients with gastric cancer [J]. Hepatogastroenterology, 2004, 51(57): 900905.
5. Sasaki H, Yukiue H, Moiriyama S, et al. Clinical significance of matrix metalloproteinase7 and Ets1 gene expression in patients with lung cancer [J]. J Surg Res, 2001, 101(2): 242247.
6. Masaki T, Matsuoka H, Sugiyama M, et al. Matrilysin (MMP7) as a significant determinant of malignant potential of early invasive colorectal carcinomas [J]. Br J Cancer, 2001, 84(10): 13171321.
7. Yamamoto H, Adachi Y, Itoh F, et al. Association of matrilysin expression with recurrence and poor prognosis in human esophageal squamous cell carcinoma [J]. Cancer Res, 1999, 59(14): 33133316.
8. Okayama H, Kumamoto K, Saitou K, et al. CD44v6, MMP7 and nuclear Cdx2 are significant biomarkers for prediction of lymph node metastasis in primary gastric cancer [J]. Oncol Rep, 2009, 22(4): 745755.
9. 黄宝俊, 徐惠绵, 赵雨杰. 应用低密度芯片初步筛选胃癌淋巴转移相关基因的研究 [J]. 中华肿瘤防治杂志, 2006, 13(24): 18411845.
10. 黄宝俊, 赵雨杰, 徐惠绵, 等. hRad17 mRNA 在胃癌中表达的意义 [J]. 中华肿瘤杂志, 2003, 25(2): 160162.
11. Wilson CL, Matrisian LM. Matrilysin: an epithelial matrix metalloproteinase with potentially novel functions [J]. Int J Biochem Cell Biol, 1996, 28(2): 123136.
12. Nishizuka I, Ichikawa Y, Ishikawa T, et al. Matrilysin stimulates DNA synthesis of cultured vascular endothelial cells and induces angiogenesis in vivo [J]. Cancer Lett, 2001, 173(2): 175182.
13. Wilson CL, Heppner KJ, Labosky PA, et al. Intestinal tumorigenesis is suppressed in mice lacking the metalloproteinase matrilysin [J]. Proc Natl Acad Sci U S A， 1997, 94(4): 14021407.
14. Goss KJ, Brown PD, Matrisian LM. Differing effects of endogenous and synthetic inhibitors of metalloproteinases on intestinal tumorigenesis [J]. Int J Cancer, 1998, 78(5): 629635.
15. Brabletz T, Jung A, Dag S, et al. betacatenin regulates the expression of the matrix metalloproteinase7 in human colorectal cancer [J]. Am J Pathol, 1999, 155(4): 10331038.
16. Ohnami S, Matsumoto N, Nakano M, et al. Identification of genes showing differential expression in antisense Krastransduced pancreatic cancer cells with suppressed tumorigenicity [J]. Cancer Res, 1999, 59(21): 55655571.
17. Fukushima H, Yamamoto H, Itoh F, et al. Association of matrilysin mRNA expression with Kras mutations and progression in pancreatic ductal adenocarcinomas [J]. Carcinogenesis, 2001, 22(7): 10491052.
18. Maruta S, Sakai H, Kanda S, et al. E1AF expression is associated with extraprostatic growth and matrix metalloproteinase7 expression in prostate cancer [J]. APMIS, 2009, 117(11): 791796.
19. Liu XP, Kawauchi S, Oga A, et al. Prognostic significance of matrix metalloproteinase7 (MMP7) expression at the invasive front in gastric carcinoma [J]. Jpn J Cancer Res, 2002, 93(3): 291295.
20. Ii M, Yamamoto H, Adachi Y, et al. Role of matrix metalloproteinase7 (matrilysin) in human cancer invasion, apoptosis, growth, and angiogenesis [J]. Exp Biol Med (Maywood), 2006, 231(1): 2027.
21. Yamashita K, Azumano I, Mai M, et al. Expression and tissue localization of matrix metalloproteinase 7 (matrilysin) in human gastric carcinomas. Implications for vessel invasion and metastasis [J]. Int J Cancer, 1998, 79(2): 187194.
22. Koskensalo S, Mrena J, Wiksten JP, et al. MMP7 overexpression is an independent prognostic marker in gastric cancer [J]. Tumour Biol, 2010, 31(3): 149155.
23. Yeh YC, Sheu BS, Cheng HC, et al. Elevated serum matrix metalloproteinase3 and 7 in H. pylorirelated gastric cancer can be biomarkers correlating with a poor survival [J]. Dig Dis Sci, 2010, 55(6): 16491657.
24. 冯众一, 徐惠绵, 黄宝俊. 基质金属蛋白酶7基因表达与胃癌生物学行为及腹膜转移的关系 [J]. 肿瘤学杂志, 2004, 10(6): 413415.
25. Yoshikawa T, Yanoma S, Tsuburaya A, et al. Expression of MMP7 and MT1MMP in peritoneal dissemination of gastric cancer [J]. Hepatogastroenterolog, 2006, 53(72): 964967.
26. Yonemura Y, Endo Y, Fujita H, et al. Inhibition of peritoneal dissemination in human gastric cancer by MMP7specific antisense oligonucleotide [J]. J Exp Clin Cancer Res, 2001, 20(2): 205212.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Expression of Matrilysin in Gastric Cancer and Its Significance: An Indicator for Determining Invasion, Metastasis, and Prognosis

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