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Published in: BMC Cancer 1/2006

Open Access 01-12-2006 | Research article

Activity and expression of urokinase-type plasminogen activator and matrix metalloproteinases in human colorectal cancer

Authors: Tae-Dong Kim, Kyoung-Sub Song, Ge Li, Hoon Choi, Hae-Duck Park, Kyu Lim, Byung-Doo Hwang, Wan-Hee Yoon

Published in: BMC Cancer | Issue 1/2006

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Abstract

Background

Matrix metalloproteinase-2 (MMP-2), matrix metalloproteinase-9 (MMP-9), and urokinase-type plasminogen activator (uPA) are involved in colorectal cancer invasion and metastasis. There is still debate whether the activity of MMP-2 and MMP-9 differs between tumors located in the colon and rectum. We designed this study to determine any differences in the expression of MMP-2, MMP-9 and uPA system between colon and rectal cancer tissues.

Methods

Cancer tissue samples were obtained from colon carcinoma (n = 12) and rectal carcinomas (n = 10). MMP-2 and MMP-9 levels were examined using gelatin zymography and Western blotting; their endogenous inhibitors, tissue inhibitor of metalloproteinase-2 (TIMP-2) and tissue inhibitor of metalloproteinase-1 (TIMP-1), were assessed by Western blotting. uPA, uPAR and PAI-1 were examined using enzyme-linked immunosorbent assay (ELISA). The activity of uPA was assessed by casein-plasminogen zymography.

Results

In both colon and rectal tumors, MMP-2, MMP-9 and TIMP-1 protein levels were higher than in corresponding paired normal mucosa, while TIMP-2 level in tumors was significantly lower than in normal mucosa. The enzyme activities or protein levels of MMP-2, MMP-9 and their endogenous inhibitors did not reach a statistically significant difference between colon and rectal cancer compared with their normal mucosa. In rectal tumors, there was an increased activity of uPA compared with the activity in colon tumors (P = 0.0266), however urokinase-type plasminogen activator receptor (uPAR) and plasminogen activator inhibitor-1 (PAI-1) showed no significant difference between colon and rectal cancer tissues.

Conclusion

These findings suggest that uPA may be expressed differentially in colon and rectal cancers, however, the activities or protein levels of MMP-2, MMP-9, TIMP-1, TIMP-2, PAI-1 and uPAR are not affected by tumor location in the colon or the rectum.
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Literature
1.
go back to reference Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, Feuer EJ, Thun MJ: Cancer statistics. CA Cancer J Clin. 2005, 55: 10-30.CrossRefPubMed Jemal A, Murray T, Ward E, Samuels A, Tiwari RC, Ghafoor A, Feuer EJ, Thun MJ: Cancer statistics. CA Cancer J Clin. 2005, 55: 10-30.CrossRefPubMed
2.
go back to reference Greenwald P: Colon cancer overview. Cancer. 1992, 70: 1206-1215. 10.1002/1097-0142(19920901)70:3+<1206::AID-CNCR2820701504>3.0.CO;2-J.CrossRefPubMed Greenwald P: Colon cancer overview. Cancer. 1992, 70: 1206-1215. 10.1002/1097-0142(19920901)70:3+<1206::AID-CNCR2820701504>3.0.CO;2-J.CrossRefPubMed
3.
go back to reference Liotta LA, Stetler-Stevenson WG: Tumor invasion and metastasis: an imbalance of positive and negative regulation. Cancer Res. 1991, 51: 5054-5059. Liotta LA, Stetler-Stevenson WG: Tumor invasion and metastasis: an imbalance of positive and negative regulation. Cancer Res. 1991, 51: 5054-5059.
4.
go back to reference Yoon WH, Jung YJ, Kim TD, Li G, Park BJ, Kim JY, Lee YC, Kim JM, Park JI, Park HD, No ZS, Lim K, Hwang BD, Kim YS: Gabexate mesilate inhibits colon cancer growth, invasion, and metastasis by reducing matrix metalloproteinases and angiogenesis. Clin Cancer Res. 2004, 10: 4517-4526. 10.1158/1078-0432.CCR-04-0084.CrossRefPubMed Yoon WH, Jung YJ, Kim TD, Li G, Park BJ, Kim JY, Lee YC, Kim JM, Park JI, Park HD, No ZS, Lim K, Hwang BD, Kim YS: Gabexate mesilate inhibits colon cancer growth, invasion, and metastasis by reducing matrix metalloproteinases and angiogenesis. Clin Cancer Res. 2004, 10: 4517-4526. 10.1158/1078-0432.CCR-04-0084.CrossRefPubMed
5.
go back to reference Sappino AP, Busso N, Belin D, Vassalli JD: Increase of urokinase-type plasminogen activator gene expression in human lung and breast carcinomas. Cancer Res. 1987, 47: 4043-4046.PubMed Sappino AP, Busso N, Belin D, Vassalli JD: Increase of urokinase-type plasminogen activator gene expression in human lung and breast carcinomas. Cancer Res. 1987, 47: 4043-4046.PubMed
6.
go back to reference Dahiya R, Yoon W, Boyle B, Schoenberg S, Yen T, Narayan P: Biochemical, cytogenetic, and morphological characteristics of human primary and metastatic prostate cancer cell lines. Biochem Int. 1992, 27: 567-577.PubMed Dahiya R, Yoon W, Boyle B, Schoenberg S, Yen T, Narayan P: Biochemical, cytogenetic, and morphological characteristics of human primary and metastatic prostate cancer cell lines. Biochem Int. 1992, 27: 567-577.PubMed
7.
go back to reference Mook ORF, Frederiks WM, Van Noorden CJF: The role of gelatinases in colorectal cancer progression and metastasis. Biochim Biophys Acta. 2004, 1705: 69-89.PubMed Mook ORF, Frederiks WM, Van Noorden CJF: The role of gelatinases in colorectal cancer progression and metastasis. Biochim Biophys Acta. 2004, 1705: 69-89.PubMed
8.
go back to reference Gomez DE, Alonso DF, Yoshiji H, Thorgeirsson UP: Tissue inhibitors of metalloproteinases: structure, regulation and biological functions. Eur J Cell Biol. 1997, 74: 111-122.PubMed Gomez DE, Alonso DF, Yoshiji H, Thorgeirsson UP: Tissue inhibitors of metalloproteinases: structure, regulation and biological functions. Eur J Cell Biol. 1997, 74: 111-122.PubMed
9.
go back to reference Andreasen PA, Kjoller L, Christensen L, Duffy MJ: The urokinase-type plasminogen activator system in cancer metastasis: a review. Int J Cancer. 1997, 72: 1-22. 10.1002/(SICI)1097-0215(19970703)72:1<1::AID-IJC1>3.0.CO;2-Z.CrossRefPubMed Andreasen PA, Kjoller L, Christensen L, Duffy MJ: The urokinase-type plasminogen activator system in cancer metastasis: a review. Int J Cancer. 1997, 72: 1-22. 10.1002/(SICI)1097-0215(19970703)72:1<1::AID-IJC1>3.0.CO;2-Z.CrossRefPubMed
10.
go back to reference Blasi F, Carmeliet P: uPAR: a versatile signalling orchestrator. Nat Rev Mol Cell Biol. 2002, 3: 932-943. 10.1038/nrm977.CrossRefPubMed Blasi F, Carmeliet P: uPAR: a versatile signalling orchestrator. Nat Rev Mol Cell Biol. 2002, 3: 932-943. 10.1038/nrm977.CrossRefPubMed
11.
go back to reference Seetoo DQ, Crowe PJ, Russell PJ, Yang JL: Quantitative expression of protein markers of plasminogen activation system in prognosis of colorectal cancer. J Surg Oncol. 2003, 82: 184-193. 10.1002/jso.10210.CrossRefPubMed Seetoo DQ, Crowe PJ, Russell PJ, Yang JL: Quantitative expression of protein markers of plasminogen activation system in prognosis of colorectal cancer. J Surg Oncol. 2003, 82: 184-193. 10.1002/jso.10210.CrossRefPubMed
12.
go back to reference Hofmann R, Lehmer A, Buresch M, Hartung R, Ulm K: Clinical relevance of urokinase plasminogen activator, its receptor, and its inhibitor in patients with renal cell carcinoma. Cancer. 1996, 78: 487-492. 10.1002/(SICI)1097-0142(19960801)78:3<487::AID-CNCR16>3.0.CO;2-V.CrossRefPubMed Hofmann R, Lehmer A, Buresch M, Hartung R, Ulm K: Clinical relevance of urokinase plasminogen activator, its receptor, and its inhibitor in patients with renal cell carcinoma. Cancer. 1996, 78: 487-492. 10.1002/(SICI)1097-0142(19960801)78:3<487::AID-CNCR16>3.0.CO;2-V.CrossRefPubMed
13.
go back to reference Duggan C, Maguire T, McDermott E, O'Higgins N, Fennelly JJ, Duffy MJ: Urokinase plasminogen activator and urokinase plasminogen activator receptor in breast cancer. Int J Cancer. 1995, 61: 597-600.CrossRefPubMed Duggan C, Maguire T, McDermott E, O'Higgins N, Fennelly JJ, Duffy MJ: Urokinase plasminogen activator and urokinase plasminogen activator receptor in breast cancer. Int J Cancer. 1995, 61: 597-600.CrossRefPubMed
14.
go back to reference Konishi K, Fujii T, Boku N, Kato S, Koba I, Ohtsu A, Tajiri H, Ochiai A, Yoshida S: Clinicopathological differences between colonic and rectal carcinomas: are they based on the same mechanism of carcinogenesis?. Gut. 1999, 45: 818-821.CrossRefPubMedPubMedCentral Konishi K, Fujii T, Boku N, Kato S, Koba I, Ohtsu A, Tajiri H, Ochiai A, Yoshida S: Clinicopathological differences between colonic and rectal carcinomas: are they based on the same mechanism of carcinogenesis?. Gut. 1999, 45: 818-821.CrossRefPubMedPubMedCentral
15.
go back to reference Kapiteijn E, Liefers GJ, Los LC, Kranenbarg EK, Hermans J, Tollenaar RA, Moriya Y, van de Velde CJ, van Krieken JH: Mechanisms of oncogenesis in colon versus rectal cancer. J Pathol. 2001, 195: 171-178. 10.1002/path.918.CrossRefPubMed Kapiteijn E, Liefers GJ, Los LC, Kranenbarg EK, Hermans J, Tollenaar RA, Moriya Y, van de Velde CJ, van Krieken JH: Mechanisms of oncogenesis in colon versus rectal cancer. J Pathol. 2001, 195: 171-178. 10.1002/path.918.CrossRefPubMed
16.
17.
go back to reference Liabakk NB, Talbot I, Smith RA, Wilkinson K, Balkwill F: Matrix metalloprotease 2 (MMP-2) and matrix metalloprotease 9 (MMP-9) type IV collagenases in colorectal cancer. Cancer Res. 1996, 56: 190-196.PubMed Liabakk NB, Talbot I, Smith RA, Wilkinson K, Balkwill F: Matrix metalloprotease 2 (MMP-2) and matrix metalloprotease 9 (MMP-9) type IV collagenases in colorectal cancer. Cancer Res. 1996, 56: 190-196.PubMed
18.
go back to reference Roeb E, Dietrich CG, Winograd R, Arndt M, Breuer B, Fass JG, Schumpelick V, Matern S: Activity and cellular origin of gelatinases in patients with colon and rectal carcinoma. Cancer. 2001, 92: 2680-2691. 10.1002/1097-0142(20011115)92:10<2680::AID-CNCR1622>3.0.CO;2-7.CrossRefPubMed Roeb E, Dietrich CG, Winograd R, Arndt M, Breuer B, Fass JG, Schumpelick V, Matern S: Activity and cellular origin of gelatinases in patients with colon and rectal carcinoma. Cancer. 2001, 92: 2680-2691. 10.1002/1097-0142(20011115)92:10<2680::AID-CNCR1622>3.0.CO;2-7.CrossRefPubMed
19.
go back to reference Bradford MM: A rapid and sensitive for the quantitation of microgram quantitites of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976, 72: 248-254. 10.1016/0003-2697(76)90527-3.CrossRefPubMed Bradford MM: A rapid and sensitive for the quantitation of microgram quantitites of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976, 72: 248-254. 10.1016/0003-2697(76)90527-3.CrossRefPubMed
20.
go back to reference Yoon WH, Song IS, Lee BH, Jung YJ, Kim TD, Li G, Lee TG, Park HD, Lim K, Hwang BD: Differential regulation of vimentin mRNA by 12-O-tetradecanoylphorbol 13-acetate and all-trans-retinoic acid correlates with motility of Hep 3B human hepatocellular carcinoma cells. Cancer Lett. 2004, 203: 99-105. 10.1016/j.canlet.2003.08.004.CrossRefPubMed Yoon WH, Song IS, Lee BH, Jung YJ, Kim TD, Li G, Lee TG, Park HD, Lim K, Hwang BD: Differential regulation of vimentin mRNA by 12-O-tetradecanoylphorbol 13-acetate and all-trans-retinoic acid correlates with motility of Hep 3B human hepatocellular carcinoma cells. Cancer Lett. 2004, 203: 99-105. 10.1016/j.canlet.2003.08.004.CrossRefPubMed
21.
go back to reference Li G, Kim DH, Kim TD, Park BJ, Park HD, Park JI, Na MK, Kim HC, Hong ND, Lim K, Hwang BD, Yoon WH: Protein-bound polysaccharide from Phellinus linteus induces G2/M phase arrest and apoptosis in SW480 human colon cancer cells. Cancer Lett. 2004, 216: 175-181. 10.1016/j.canlet.2004.07.014.CrossRefPubMed Li G, Kim DH, Kim TD, Park BJ, Park HD, Park JI, Na MK, Kim HC, Hong ND, Lim K, Hwang BD, Yoon WH: Protein-bound polysaccharide from Phellinus linteus induces G2/M phase arrest and apoptosis in SW480 human colon cancer cells. Cancer Lett. 2004, 216: 175-181. 10.1016/j.canlet.2004.07.014.CrossRefPubMed
22.
go back to reference Pesta M, Holubec LJ, Topolcan O, Cerna M, Rupert K, Holubec LS, Treska V, Kormunda S, Elgrova L, Finek J, Cerny R: Quantitative estimation of matrix metalloproteinases 2 and 7 (MMP-2, MMP-7) and tissue inhibitors of matrix metalloproteinases 1 and 2 (TIMP-1, TIMP-2) in colorectal carcinoma tissue samples. Anticancer Res. 2005, 25: 3387-3391.PubMed Pesta M, Holubec LJ, Topolcan O, Cerna M, Rupert K, Holubec LS, Treska V, Kormunda S, Elgrova L, Finek J, Cerny R: Quantitative estimation of matrix metalloproteinases 2 and 7 (MMP-2, MMP-7) and tissue inhibitors of matrix metalloproteinases 1 and 2 (TIMP-1, TIMP-2) in colorectal carcinoma tissue samples. Anticancer Res. 2005, 25: 3387-3391.PubMed
23.
go back to reference Baker EA, Leaper DJ: The plasminogen activator and matrix metalloproteinase systems in colorectal cancer: relationship to tumour pathology. Eur J Cancer. 2003, 39: 981-988. 10.1016/S0959-8049(03)00065-0.CrossRefPubMed Baker EA, Leaper DJ: The plasminogen activator and matrix metalloproteinase systems in colorectal cancer: relationship to tumour pathology. Eur J Cancer. 2003, 39: 981-988. 10.1016/S0959-8049(03)00065-0.CrossRefPubMed
24.
go back to reference Stetler-Stevenson WG, Brown PD, Onisto M, Levy AT, Liotta LA: Tissue inhibitor of metalloproteinases-2 (TIMP-2) mRNA expression in tumor cell lines and human tumor tissues. J Biol Chem. 1990, 265: 13933-13938.PubMed Stetler-Stevenson WG, Brown PD, Onisto M, Levy AT, Liotta LA: Tissue inhibitor of metalloproteinases-2 (TIMP-2) mRNA expression in tumor cell lines and human tumor tissues. J Biol Chem. 1990, 265: 13933-13938.PubMed
25.
go back to reference Li BH, Zhao P, Liu SZ, Yu YM, Han M, Wen JK: Matrix metalloproteinase-2 and tissue inhibitor of metallo-proteinase-2 in colorectal carcinoma invasion and metastasis. World J Gastroenterol. 2005, 28: 3046-3050.CrossRef Li BH, Zhao P, Liu SZ, Yu YM, Han M, Wen JK: Matrix metalloproteinase-2 and tissue inhibitor of metallo-proteinase-2 in colorectal carcinoma invasion and metastasis. World J Gastroenterol. 2005, 28: 3046-3050.CrossRef
26.
go back to reference Grondahl-Hansen J, Ralfkiaer E, Kirkeby L, Kristensen P, Lund L, Dano K: Localization of urokinase-type plasminogen activator in stromal cells in adenocarcinomas of the colon in humans. Am J Pathol. 1991, 138: 111-117.PubMedPubMedCentral Grondahl-Hansen J, Ralfkiaer E, Kirkeby L, Kristensen P, Lund L, Dano K: Localization of urokinase-type plasminogen activator in stromal cells in adenocarcinomas of the colon in humans. Am J Pathol. 1991, 138: 111-117.PubMedPubMedCentral
27.
go back to reference Costantini V, Sidoni A, Deveglia R, Cazzato O, Bellezza G, Ferri I, Bucciarelli E, Nenci G: Combined overexpression of urokinase, urokinase receptor, and plasminogen activator inhibitor-1 is associated with breast cancer progression: an immunohistochemical comparison of normal, benign, and malignant breast tissues. Cancer. 1996, 77: 1079-1088. 10.1002/(SICI)1097-0142(19960315)77:6<1079::AID-CNCR12>3.0.CO;2-Z.CrossRefPubMed Costantini V, Sidoni A, Deveglia R, Cazzato O, Bellezza G, Ferri I, Bucciarelli E, Nenci G: Combined overexpression of urokinase, urokinase receptor, and plasminogen activator inhibitor-1 is associated with breast cancer progression: an immunohistochemical comparison of normal, benign, and malignant breast tissues. Cancer. 1996, 77: 1079-1088. 10.1002/(SICI)1097-0142(19960315)77:6<1079::AID-CNCR12>3.0.CO;2-Z.CrossRefPubMed
28.
go back to reference Harvey SR, Sait SNJ, Xu Y, Bailey JL, Penetrante RM, Markus G: Demonstration of urokinase expression in cancer cells of colon adenocarcinomas by immunohistochemistry and in situ hybridization. Am J Pathol. 1999, 155: 1115-1120.CrossRefPubMedPubMedCentral Harvey SR, Sait SNJ, Xu Y, Bailey JL, Penetrante RM, Markus G: Demonstration of urokinase expression in cancer cells of colon adenocarcinomas by immunohistochemistry and in situ hybridization. Am J Pathol. 1999, 155: 1115-1120.CrossRefPubMedPubMedCentral
29.
go back to reference Berger DH: Plasmin/Plasminogen system in colorectal cancer. World J Surg. 2002, 26: 767-771. 10.1007/s00268-002-4050-8.CrossRefPubMed Berger DH: Plasmin/Plasminogen system in colorectal cancer. World J Surg. 2002, 26: 767-771. 10.1007/s00268-002-4050-8.CrossRefPubMed
30.
go back to reference Wang W, Abbruzzese JL, Evans DB, Chiao PJ: Overexpression of urokinase-type plasminogen activator in pancreatic adenocarcinoma is regulated by constitutively activated RelA. Oncogene. 1999, 18: 4554-4563. 10.1038/sj.onc.1202833.CrossRefPubMed Wang W, Abbruzzese JL, Evans DB, Chiao PJ: Overexpression of urokinase-type plasminogen activator in pancreatic adenocarcinoma is regulated by constitutively activated RelA. Oncogene. 1999, 18: 4554-4563. 10.1038/sj.onc.1202833.CrossRefPubMed
31.
go back to reference Singh B, Berry J, Shoher A, Ramakrishnan V, Lucci A: COX-2 overexpression increases motility and invasion of breast cancer cells. Int J Oncol. 2005, 26: 1393-1399.PubMed Singh B, Berry J, Shoher A, Ramakrishnan V, Lucci A: COX-2 overexpression increases motility and invasion of breast cancer cells. Int J Oncol. 2005, 26: 1393-1399.PubMed
32.
go back to reference Sakakibara T, Hibi K, Koike M, Fujiwara M, Kodera Y, Ito K, Nakao A: Plasminogen activator inhibitor-1 as a potential marker for the malignancy of colorectal cancer. Br J Cancer. 2005, 93: 799-803. 10.1038/sj.bjc.6602743.CrossRefPubMedPubMedCentral Sakakibara T, Hibi K, Koike M, Fujiwara M, Kodera Y, Ito K, Nakao A: Plasminogen activator inhibitor-1 as a potential marker for the malignancy of colorectal cancer. Br J Cancer. 2005, 93: 799-803. 10.1038/sj.bjc.6602743.CrossRefPubMedPubMedCentral
Metadata
Title
Activity and expression of urokinase-type plasminogen activator and matrix metalloproteinases in human colorectal cancer
Authors
Tae-Dong Kim
Kyoung-Sub Song
Ge Li
Hoon Choi
Hae-Duck Park
Kyu Lim
Byung-Doo Hwang
Wan-Hee Yoon
Publication date
01-12-2006
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2006
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-6-211

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