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Published in: International Journal of Colorectal Disease 6/2004

01-11-2004 | Original Article

Simultaneous determination of matrix metalloproteinase (MMP)-7, MMP-1, -3, and -13 gene expression by multiplex PCR in colorectal carcinomas

Authors: Elke Roeb, Marlies Arndt, Bettina Jansen, Volker Schumpelick, Siegfried Matern

Published in: International Journal of Colorectal Disease | Issue 6/2004

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Abstract

Background and aims

MMP-7, a member of the matrix metalloproteinase family, is believed to play a significant role in the growth and proliferation of colon cancer cells. The aim of this study was to evaluate MMP-7 gene expression in comparison with MMP-1, MMP-3, and MMP-13 in patients with resectable rectal and colon cancer by a semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR).

Materials and methods

Biopsy samples of tumor (n=30) and distant normal mucosa (n=30) from 30 patients were obtained intraoperation. Messenger (m)RNA was extracted from all of the tissue samples and reverse transcribed to double-stranded cDNA. Semi-quantitative RT-PCR was performed to study the MMP gene expression in both the tumor and normal mucosal specimens. MMP mRNA values were expressed relative to glyceraldehyde-3-phosphate dehydrogenase (GAPDH) for each sample.

Results

In all 30 cases an increase in MMP-7 mRNA expression was detected in the cancerous tissue (p=0.00004). In 21 out of 30 cases an increase in MMP-13 mRNA (p=0.023) and in 22 out of 30 cases an increase in MMP-3 mRNA (p=0.075) was detected in the cancerous tissue. In contrast, there was no significant change in the MMP-1 expression of normal and cancerous mucosal specimens in either colon or rectal carcinomas. There were no significant differences between rectum and colon carcinomas.

Conclusion

Taking into account our earlier studies, we conclude that most cases of colorectal carcinogenesis are characterized by enhanced expression of MMP-7, -13, -3 and the gelatinases, whereas MMP-1-expression is very inconsistent and not overexpressed in many cases. MMP-7 inhibition as well as inhibition of MMP-13 and MMP-3 may be a useful preventive or therapeutic adjunct in colorectal cancer.
Literature
1.
go back to reference Sternlicht MD, Werb Z (2001) How matrix metalloproteinases regulate cell behavior. Annu Rev Cell Dev Biol 17:463–516CrossRefPubMed Sternlicht MD, Werb Z (2001) How matrix metalloproteinases regulate cell behavior. Annu Rev Cell Dev Biol 17:463–516CrossRefPubMed
2.
go back to reference Visse R, Nagase H (2003) Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res 92:827–839CrossRefPubMed Visse R, Nagase H (2003) Matrix metalloproteinases and tissue inhibitors of metalloproteinases: structure, function, and biochemistry. Circ Res 92:827–839CrossRefPubMed
3.
go back to reference Curran S, Murray GI (2000) Matrix metalloproteinases: molecular aspects of their roles in tumour invasion and metastasis. Eur J Cancer 36:1621–1630PubMed Curran S, Murray GI (2000) Matrix metalloproteinases: molecular aspects of their roles in tumour invasion and metastasis. Eur J Cancer 36:1621–1630PubMed
4.
go back to reference Itoh Y, Nagase H (2002) Matrix metalloproteinases in cancer. Essays Biochem 38:21–36PubMed Itoh Y, Nagase H (2002) Matrix metalloproteinases in cancer. Essays Biochem 38:21–36PubMed
5.
go back to reference Yu AE, Hewitt RE, Connor EW, Stetler-Stevenson WG (1997) Matrix metalloproteinases. Novel targets for directed cancer therapy. Drugs Aging 11:229–244PubMed Yu AE, Hewitt RE, Connor EW, Stetler-Stevenson WG (1997) Matrix metalloproteinases. Novel targets for directed cancer therapy. Drugs Aging 11:229–244PubMed
6.
go back to reference Nabeshima K, Inoue T, Shimao Y, Sameshima T (2002) Matrix metalloproteinases in tumor invasion: role for cell migration. Pathol Int 52:255–264CrossRefPubMed Nabeshima K, Inoue T, Shimao Y, Sameshima T (2002) Matrix metalloproteinases in tumor invasion: role for cell migration. Pathol Int 52:255–264CrossRefPubMed
7.
go back to reference Gearing AJ, Beckett P, Christodoulou M, Churchill M, Clements J, Davidson AH, Drummond AH, Galloway WA, Gilbert R, Gordon JL, Leber TM, Mangan M, Miller K, Nayee P, Owen K, Patel S, Thomas W, Wells G, Wood LM, Woolley K (1994) Processing of tumour necrosis factor-alpha precursor by metalloproteinases. Nature 370:555–557PubMed Gearing AJ, Beckett P, Christodoulou M, Churchill M, Clements J, Davidson AH, Drummond AH, Galloway WA, Gilbert R, Gordon JL, Leber TM, Mangan M, Miller K, Nayee P, Owen K, Patel S, Thomas W, Wells G, Wood LM, Woolley K (1994) Processing of tumour necrosis factor-alpha precursor by metalloproteinases. Nature 370:555–557PubMed
8.
go back to reference Overall CM, McQuibban GA, Clark-Lewis I (2002) Discovery of chemokine substrates for matrix metalloproteinases by exosite scanning: a new tool for degradomics. Biol Chem 383:1059–1066PubMed Overall CM, McQuibban GA, Clark-Lewis I (2002) Discovery of chemokine substrates for matrix metalloproteinases by exosite scanning: a new tool for degradomics. Biol Chem 383:1059–1066PubMed
9.
go back to reference Van den Steen PE, Proost P, Grillet B, Brand DD, Kang AH, Van Damme J, Opdenakker G (2002) Cleavage of denatured natural collagen type II by neutrophil gelatinase B reveals enzyme specificity, post-translational modifications in the substrate, and the formation of remnant epitopes in rheumatoid arthritis. FASEB J 16:379–389CrossRefPubMed Van den Steen PE, Proost P, Grillet B, Brand DD, Kang AH, Van Damme J, Opdenakker G (2002) Cleavage of denatured natural collagen type II by neutrophil gelatinase B reveals enzyme specificity, post-translational modifications in the substrate, and the formation of remnant epitopes in rheumatoid arthritis. FASEB J 16:379–389CrossRefPubMed
10.
go back to reference Roeb E, Behrmann I, Grötzinger J, Breuer B, Matern S (2000) A MMP-9 mutant without gelatinolytic activity as a novel TIMP-1-antagonist. FASEB J 14:1671–1673PubMed Roeb E, Behrmann I, Grötzinger J, Breuer B, Matern S (2000) A MMP-9 mutant without gelatinolytic activity as a novel TIMP-1-antagonist. FASEB J 14:1671–1673PubMed
11.
go back to reference Roeb E, Schleinkofer K, Kernebeck T, Poetsch S, Behrmann I, Jansen B, Matern S, Grötzinger J (2002) The MMP-9 hemopexin domain is a novel gelatin binding domain and acts as an antagonist. J Biol Chem 277:50326–50332CrossRefPubMed Roeb E, Schleinkofer K, Kernebeck T, Poetsch S, Behrmann I, Jansen B, Matern S, Grötzinger J (2002) The MMP-9 hemopexin domain is a novel gelatin binding domain and acts as an antagonist. J Biol Chem 277:50326–50332CrossRefPubMed
12.
go back to reference Mysliwiec AG, Ornstein DL (2002) Matrix metalloproteinases in colorectal cancer. Clin Colorectal Cancer 1:208–219PubMed Mysliwiec AG, Ornstein DL (2002) Matrix metalloproteinases in colorectal cancer. Clin Colorectal Cancer 1:208–219PubMed
13.
go back to reference Murray GI, Duncan ME, O’Neil P, Melvin WT, Fothergill JE (1996) Matrix metalloproteinase-1 is associated with poor prognosis in colorectal cancer. Nat Med 2:461–462PubMed Murray GI, Duncan ME, O’Neil P, Melvin WT, Fothergill JE (1996) Matrix metalloproteinase-1 is associated with poor prognosis in colorectal cancer. Nat Med 2:461–462PubMed
14.
go back to reference Zeng ZS, Huang Y, Cohen AM, Guillem JG (1996) Prediction of colorectal cancer relapse and survival via tissue RNA levels of matrix metalloproteinase-9. J Clin Oncol 14:3133–3140PubMed Zeng ZS, Huang Y, Cohen AM, Guillem JG (1996) Prediction of colorectal cancer relapse and survival via tissue RNA levels of matrix metalloproteinase-9. J Clin Oncol 14:3133–3140PubMed
15.
go back to reference Adachi Y, Yamamoto H, Itoh F, Hinoda Y, Okada Y, Imai K (1999) Contribution of matrilysin (MMP-7) to the metastatic pathway of human colorectal cancers. Gut 45:252–258PubMed Adachi Y, Yamamoto H, Itoh F, Hinoda Y, Okada Y, Imai K (1999) Contribution of matrilysin (MMP-7) to the metastatic pathway of human colorectal cancers. Gut 45:252–258PubMed
16.
go back to reference Kikuchi R, Noguchi T, Takeno S, Kubo N, Uchida Y (2000) Immunohistochemical detection of membrane-type-1-matrix metalloproteinase in colorectal carcinoma. Br J Cancer 83:215–218CrossRefPubMed Kikuchi R, Noguchi T, Takeno S, Kubo N, Uchida Y (2000) Immunohistochemical detection of membrane-type-1-matrix metalloproteinase in colorectal carcinoma. Br J Cancer 83:215–218CrossRefPubMed
17.
go back to reference Sardinha TC, Nogueras JJ, Xiong H, Weiss EG, Wexner SD, Abramson S (2000) Membrane-type 1 matrix metalloproteinase mRNA expression in colorectal cancer. Dis Colon Rectum 43:389–395PubMed Sardinha TC, Nogueras JJ, Xiong H, Weiss EG, Wexner SD, Abramson S (2000) Membrane-type 1 matrix metalloproteinase mRNA expression in colorectal cancer. Dis Colon Rectum 43:389–395PubMed
18.
go back to reference Roeb E, Dietrich CG, Winograd R, Arndt M, Breuer B, Faß J, Schumpelick V, Matern S (2001) Activity and cellular origin of gelatinases in colon and rectal cancer: differential activity of MMP-9. Cancer 92:2680–2691CrossRefPubMed Roeb E, Dietrich CG, Winograd R, Arndt M, Breuer B, Faß J, Schumpelick V, Matern S (2001) Activity and cellular origin of gelatinases in colon and rectal cancer: differential activity of MMP-9. Cancer 92:2680–2691CrossRefPubMed
19.
go back to reference Leeman MF, McKay JA, Murray GI (2002) Matrix metalloproteinase 13 activity is associated with poor prognosis in colorectal cancer. J Clin Pathol 55:758–762CrossRefPubMed Leeman MF, McKay JA, Murray GI (2002) Matrix metalloproteinase 13 activity is associated with poor prognosis in colorectal cancer. J Clin Pathol 55:758–762CrossRefPubMed
20.
go back to reference Roeb E, Purucker E, Breuer B, Nguyen HN, Heinrich PC, Rose-John S, Matern S (1997) TIMP expression in toxic and cholestatic liver injury in rats. J Hepatol 27:535–544CrossRef Roeb E, Purucker E, Breuer B, Nguyen HN, Heinrich PC, Rose-John S, Matern S (1997) TIMP expression in toxic and cholestatic liver injury in rats. J Hepatol 27:535–544CrossRef
21.
go back to reference Yamashita K, Azumano I, Mai M, Okada Y (1998) Expression and tissue localization of matrix metalloproteinase 7 (matrilysin) in human gastric carcinomas. Implication for vessel invasion and metastasis. Int J Cancer 79:187–194CrossRefPubMed Yamashita K, Azumano I, Mai M, Okada Y (1998) Expression and tissue localization of matrix metalloproteinase 7 (matrilysin) in human gastric carcinomas. Implication for vessel invasion and metastasis. Int J Cancer 79:187–194CrossRefPubMed
22.
go back to reference Masaki T, Matsuoka H, Sugiyama M, Abe N, Goto A, Sakamoto A, Atomi Y (2001) Matrilysin (MMP-7) as a significant determinant of malignant potential of early invasive colorectal carcinomas. Br J Cancer 84:1317–1321CrossRefPubMed Masaki T, Matsuoka H, Sugiyama M, Abe N, Goto A, Sakamoto A, Atomi Y (2001) Matrilysin (MMP-7) as a significant determinant of malignant potential of early invasive colorectal carcinomas. Br J Cancer 84:1317–1321CrossRefPubMed
23.
go back to reference Yamamoto H, Itoh F, Hinoda Y, Senota A, Yoshimoto M, Nakamura H, Imai K, Yachi A (1994) Expression of matrilysin mRNA in colorectal adenomas and its induction by truncated fibronectin. Biochem Biophys Res Commun 201:657–664CrossRefPubMed Yamamoto H, Itoh F, Hinoda Y, Senota A, Yoshimoto M, Nakamura H, Imai K, Yachi A (1994) Expression of matrilysin mRNA in colorectal adenomas and its induction by truncated fibronectin. Biochem Biophys Res Commun 201:657–664CrossRefPubMed
24.
go back to reference Wilson CL, Matrisian LM (1996) Matrilysin: an epithelial matrix metalloproteinase with potentially novel functions. Int J Biochem Cell Biol 28:123–136CrossRefPubMed Wilson CL, Matrisian LM (1996) Matrilysin: an epithelial matrix metalloproteinase with potentially novel functions. Int J Biochem Cell Biol 28:123–136CrossRefPubMed
25.
go back to reference Crabbe T, Smith B, O’Connell J, Docherty A (1994) Human progelatinase A can be activated by matrilysin. FEBS Lett 345:14–16CrossRefPubMed Crabbe T, Smith B, O’Connell J, Docherty A (1994) Human progelatinase A can be activated by matrilysin. FEBS Lett 345:14–16CrossRefPubMed
26.
go back to reference Imai K, Yokohama Y, Nakanishi I, Ohuchi E, Fujii Y, Nakai N, Okada Y (1995) Matrix metalloproteinase 7 (matrilysin) from human rectal carcinoma cells. Activation of the precursor, interaction with other matrix metalloproteinases and enzymatic properties. J Biol Chem 270:6691–6697CrossRefPubMed Imai K, Yokohama Y, Nakanishi I, Ohuchi E, Fujii Y, Nakai N, Okada Y (1995) Matrix metalloproteinase 7 (matrilysin) from human rectal carcinoma cells. Activation of the precursor, interaction with other matrix metalloproteinases and enzymatic properties. J Biol Chem 270:6691–6697CrossRefPubMed
27.
go back to reference Witty JP, McDonnell S, Newell KJ, Cannon P, Navre M, Tressler RJ, Matrisian LM (1994) Modulation of matrilysin levels in colon carcinoma cell lines affects tumorigenicity in vivo. Cancer Res 54:4805–4812PubMed Witty JP, McDonnell S, Newell KJ, Cannon P, Navre M, Tressler RJ, Matrisian LM (1994) Modulation of matrilysin levels in colon carcinoma cell lines affects tumorigenicity in vivo. Cancer Res 54:4805–4812PubMed
28.
go back to reference Heppner KJ, Matrisian LM, Jensen RA, Rodgers WH (1996) Expression of most matrix metalloproteinase family members in breast cancer represents a tumour-induced host response. Am J Pathol 149:273–282PubMed Heppner KJ, Matrisian LM, Jensen RA, Rodgers WH (1996) Expression of most matrix metalloproteinase family members in breast cancer represents a tumour-induced host response. Am J Pathol 149:273–282PubMed
29.
go back to reference Airola K, Karonen T, Vaalamo M, Lehti K, Lohi J, Kariniemi AL, Keski-Oja J, Saarialho-Kere UK (1999) Expression of collagenases-1 and −3 and their inhibitors TIMP-1 and -3 correlates with the level of invasion in malignant melanomas. Br J Cancer 80:733–743CrossRefPubMed Airola K, Karonen T, Vaalamo M, Lehti K, Lohi J, Kariniemi AL, Keski-Oja J, Saarialho-Kere UK (1999) Expression of collagenases-1 and −3 and their inhibitors TIMP-1 and -3 correlates with the level of invasion in malignant melanomas. Br J Cancer 80:733–743CrossRefPubMed
30.
go back to reference Newell KJ, Witty JP, Rodgers WH, Matrisian LM (1994) Expression and localization of matrix-degrading metalloproteinases during colorectal tumorigenesis. Mol Carcinog 10:199–206PubMed Newell KJ, Witty JP, Rodgers WH, Matrisian LM (1994) Expression and localization of matrix-degrading metalloproteinases during colorectal tumorigenesis. Mol Carcinog 10:199–206PubMed
31.
go back to reference Harris ED Jr, Krane SM (1974) Collagenases (second of three parts). N Engl J Med 291:605–609PubMed Harris ED Jr, Krane SM (1974) Collagenases (second of three parts). N Engl J Med 291:605–609PubMed
32.
go back to reference Shiozawa J, Ito M, Nakayama T, Nakashima M, Kohno S, Sekine I (2000) Expression of matrix metalloproteinase-1 in human colorectal carcinoma. Mod Pathol 13:925–933PubMed Shiozawa J, Ito M, Nakayama T, Nakashima M, Kohno S, Sekine I (2000) Expression of matrix metalloproteinase-1 in human colorectal carcinoma. Mod Pathol 13:925–933PubMed
33.
go back to reference Sunami E, Tsuno N, Osada T, Saito S, Kitayama J, Tomozawa S, Tsuruo T, Shibata Y, Muto T, Nagawa H (2000) MMP-1 is a prognostic marker for hematogenous metastasis of colorectal cancer. Oncologist 5:108–114PubMed Sunami E, Tsuno N, Osada T, Saito S, Kitayama J, Tomozawa S, Tsuruo T, Shibata Y, Muto T, Nagawa H (2000) MMP-1 is a prognostic marker for hematogenous metastasis of colorectal cancer. Oncologist 5:108–114PubMed
34.
go back to reference Nakopoulou L, Giannopoulou I, Gakiopoulou H, Liapis H, Tzonou A, Davaris PS (1999) Matrix metalloproteinase-1 and -3 in breast cancer: correlation with progesterone receptors and other clinicopathologic features. Hum Pathol 30:436–442PubMed Nakopoulou L, Giannopoulou I, Gakiopoulou H, Liapis H, Tzonou A, Davaris PS (1999) Matrix metalloproteinase-1 and -3 in breast cancer: correlation with progesterone receptors and other clinicopathologic features. Hum Pathol 30:436–442PubMed
Metadata
Title
Simultaneous determination of matrix metalloproteinase (MMP)-7, MMP-1, -3, and -13 gene expression by multiplex PCR in colorectal carcinomas
Authors
Elke Roeb
Marlies Arndt
Bettina Jansen
Volker Schumpelick
Siegfried Matern
Publication date
01-11-2004
Publisher
Springer-Verlag
Published in
International Journal of Colorectal Disease / Issue 6/2004
Print ISSN: 0179-1958
Electronic ISSN: 1432-1262
DOI
https://doi.org/10.1007/s00384-004-0592-6

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