대장암 조직에서 Matrix Matalloproteinase-2, -7, -9,-12의 발현과 임상적인 의의 = The Expression and Clinical Correlations of Matrix Metalloproteinase-2, -7, -9, and -12 in Colorectal Cancer

다국어 초록 (Multilingual Abstract)

Purpose: Tumor invasion and metastasis are multistep phenomina, involving proteolytic degradation of extracellular matrix
(ECM) and alteration of cell adhesion. It is another oncologic therapeutic strategy to block tumor invasion and metastasis
through analyzing the molecules which are involved in these processes. We examined the expressions of some of matrix
metalloproteinases (MMPs) in colorectal cancer and analyze the correlation with clinical factors and survival.
Methods: Fifty-five patients with colorectal cancer who underwent surgical resection were included. The expressions of the
MMP-2, -7, -9, and -12 in tumor tissue and normal mucosa using RT-PCR technique was carried out. We evaluated and
analyzed the correlation among these molecules, clinical characteristics, and survival.
Results: Expressions of MMP-7, -9, and -12 were significantly higher in tumor tissue than in normal mucosa (P=0.00). The
expressions of MMP-2 between cancer and normal mucosa had no significant difference but it had a significant difference
according to the lymph node (LN) invasion (P=0.03) in tumor tissues. Three-year overall survival was worse in patient with high
expression of MMP-2 compared to low expression.
Conclusion: The expressions of MMP-7, -9, -12 in tumor tissue were higher than in normal mucosa and MMP-2 expression
of tumor tissues had a significant difference according to LN invasion. MMP-2 overexpression seems to be a prognostic
factor for 3-yr overall survival. But, large scale study with long term survival analysis will be needed for the prognostic
significance of MMPs.

다국어 초록 (Multilingual Abstract)

Purpose: Tumor invasion and metastasis are multistep phenomina, involving proteolytic degradation of extracellular matrix
(ECM) and alteration of cell adhesion. It is another oncologic therapeutic strategy to block tumor invasion and metastasis
through analyzing the molecules which are involved in these processes. We examined the expressions of some of matrix
metalloproteinases (MMPs) in colorectal cancer and analyze the correlation with clinical factors and survival.
Methods: Fifty-five patients with colorectal cancer who underwent surgical resection were included. The expressions of the
MMP-2, -7, -9, and -12 in tumor tissue and normal mucosa using RT-PCR technique was carried out. We evaluated and
analyzed the correlation among these molecules, clinical characteristics, and survival.
Results: Expressions of MMP-7, -9, and -12 were significantly higher in tumor tissue than in normal mucosa (P=0.00). The
expressions of MMP-2 between cancer and normal mucosa had no significant difference but it had a significant difference
according to the lymph node (LN) invasion (P=0.03) in tumor tissues. Three-year overall survival was worse in patient with high
expression of MMP-2 compared to low expression.
Conclusion: The expressions of MMP-7, -9, -12 in tumor tissue were higher than in normal mucosa and MMP-2 expression
of tumor tissues had a significant difference according to LN invasion. MMP-2 overexpression seems to be a prognostic
factor for 3-yr overall survival. But, large scale study with long term survival analysis will be needed for the prognostic
significance of MMPs.

참고문헌 (Reference)

1 Tryggvason K, "Type IV collagenases in invasive tumors" 24 : 209-218, 1993

2 Stetler-Stevenson WG, "Tissue inhibitor of metalloproteinase (TIMP-2): a new member of the metalloproteinase inhibitor family" 264 : 17374-17378, 1989

3 Gallegos NC, "The distribution of matrix metalloproteinases and tissue inhibitor of metalloproteinases in colorectal cancer" 4 : 111-119, 1995

4 Zucker S, "Role of matrix metalloproteinases (MMPs) in colorectal cancer" 23 : 101-117, 2004

5 Asano T, "Prognostic values of matrix metalloproteinase family expression in human colorectal carcinoma" 146 : 32-42, 2008

6 Zeng ZS, "Prediction of colorectal cancer relapse and survival via tissue RNA levels of matrix metalloproteinase-9" 14 : 3133-3140, 1996

7 Pyke C, "Messenger RNA for two type IV collagenases is located in stromal cells in human colon cancer" 142 : 359-365, 1993

8 Curran S, "Matrix metalloproteinases: molecular aspects of their roles in tumour invasion and metastasis" 36 : 1621-1630, 2000

9 Wagenaar-Miller RA, "Matrix metalloproteinases in colorectal cancer: is it worth talking about?" 23 : 119-135, 2004

10 Vihinen P, "Matrix metalloproteinases in cancer: prognostic markers and therapeutic targets" 99 : 157-166, 2002

11 Stetler-Stevenson WG, "Matrix metalloproteinases and tumor invasion: from correlation and causality to the clinic" 7 : 147-154, 1996

12 Li BH, "Matrix metalloproteinase-2 and tissue inhibitor of metalloproteinase-2 in colorectal carcinoma invasion and metastasis" 11 : 3046-3050, 2005

13 Takeuchi N, "Matrilysin gene expression in sporadic and familial colorectal adenomas" 19 : 225-229, 1997

14 Masaki T, "Matrilysin (MMP-7) as a significant determinant of malignant potential of early invasive colorectal carcinomas" 84 : 1317-1321, 2001

15 Dong Z, "Macrophage-derived metalloelastase is responsible for the generation of angiostatin in Lewis lung carcinoma" 88 : 801-810, 1997

16 Langenskiold M, "Increased plasma MMP-2 protein expression in lymph node-positive patients with colorectal cancer" 20 : 245-252, 2005

17 Yang W, "Human macrophage metalloelastase gene expression in colorectal carcinoma and its clinicopathologic significance" 91 : 1277-1283, 2001

18 Parsons SL, "Gelatinase (MMP-2 and -9) expression in gastrointestinal malignancy" 78 : 1495-1502, 1998

19 Ring P, "Expression of tissue inhibitor of metalloproteinases TIMP-2 in human colorectal cancer-a predictor of tumour stage" 76 : 805-811, 1997

20 Papadopoulou S, "Expression of gelatinase-A (MMP-2) in human colon cancer and normal colon mucosa" 22 : 383-389, 2001

21 McDonnell S, "Expression and localization of the matrix metalloproteinase pump-1 (MMP-7) in human gastric and colon carcinomas" 4 : 527-533, 1991

22 Newell KJ, "Expression and localization of matrix-degrading metalloproteinases during colorectal tumorigenesis" 10 : 199-206, 1994

23 Adachi Y, "Contribution of matrilysin (MMP-7) to the metastatic pathway of human colorectal cancers" 45 : 252-258, 1999

24 Adachi Y, "Clinicopathologic and prognostic significance of matrilysin expression at the invasive front in human colorectal cancers" 95 : 290-294, 2001

25 Chambers AF, "Changing views of the role of matrix metalloproteinases in metastasis" 89 : 1260-1270, 1997