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2008 | 55 | 2 | 357-363
Article title

Antigen levels of urokinase-type plasminogen activator receptor and its gene polymorphism related to microvessel density in colorectal cancer

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We determined the distribution of genotypes and frequencies of alleles of the (CA)n repeat polymorphism in intron 3 of the urokinase plasminogen activator receptor (uPAR) gene, uPAR antigen levels and microvessel density (MVD) in tumour and distant mucosa samples from 52 patients with colorectal cancer. The uPAR level was higher for patients with high MVD comparing to patients with lower MVD which may suggest that uPAR can be correlated with progression of colorectal cancer. The significant relationship between the high MVD and uPAR antigen level appeared to be independent of the (CA)n repeat polymorphism because no differences in the level of uPAR antigen between carriers of alleles were found. The received results, indicate that uPAR might be considered as a target in colorectal cancer patients' therapy.
Physical description
  • Department of Molecular Genetics, University of Lodz, Łódź, Poland
  • Department of Medical Biochemistry, Medical University in Lodz, Łódź, Poland
  • Polish Mother's Memorial Hospital - Research Institute, Łódź, Poland
  • Department of General and Colorectal Surgery, Medical University of Lodz, Łódź, Poland
  • 2nd Department of Surgery, Medical University of Lodz, Łódź, Poland
  • Department of Molecular Genetics, University of Lodz, Łódź, Poland
  • Baker EA, Bergin FG, Leaper DJ (2000) Plasminogen activator system, vascular endothelial growth factor, and colorectal cancer progression. Mol Pathol 53: 307-312.
  • Baker EA, Leaper DJ (2003) The plasminogen activator and matrix metalloproteinase systems in colorectal cancer: relationship to tumour pathology. Eur J Cancer 39: 981-988.
  • Błasiak J, Smolarz B (2003) Plasminogen activator inhibitor-1 (PAI-1) gene 4G/5G promoter polymorphism is not associated with breast cancer. Acta Biochim Polon 47: 191-109.
  • Błasiak J, Smolarz B, Romanowicz-Makowska H, Pertyński T (2000): Plasminogen activator inhibitor-1 (PAI-1) promoter 4G/5G genotype in postmenopausal women with breast cancer. Pol J Gyneacol Invest 2: 149-154.
  • Borglum AD, Byskov A, Cubellis MV, Kruse TA (1991) An EcoRI polymorphism for the PLAUR gene. Nucleic Acids Res 19: 6661.
  • Borglum AD, Byskov A, Roldan AL, Kruse TA (1992) Two PstI polymorphisms for the urokinase-type plasminogen activator receptor gene (PLAUR). Hum Genet 89: 584.
  • Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-day binding. Anal Biochem 72: 248-256.
  • Dkhissi F, Lu H, Soria C, Opolon P, Griscelli F, Liu H, Khattar P, Mishal Z, Perricaudet M, Li H (2003) Endostatin exhibits a direct antitumor effect in addition to its antiangiogenic activity in colon cancer cells. Hum Gene Ther 14: 997-1008.
  • Eriksson P, Kallin B, van't Hooft F, Bavenholm P, Hamsten A (1995) Allele-specific increase in basal transcription of the plasminogen-activator inhibitor 1 gene is associated with myocardial infraction. Proc Natl Acad Sci USA 92: 1851-1855.
  • Gillette KM, Forbes K, Sehgal I (2003) Detection of matrix metalloproteinases (MMP), tissue inhibitor of metalloproteinase-2, urokinase and plasminogen activator inhibitor-1 within matrigel and growth factor-reduced matrigel basement membrane. Tumori 89: 421-425.
  • Hamsten A, de Faire U, Walldius G, Dahlen G, Syamosi A, Landou C, Blomback M, Wiman B (1987) Plasminogen activator inhibitor in plasma: risk factor for recurrent myocardial infarction. Lancet 2: 3-9.
  • Hildenbrand R, Dilger I, Horlin A, Stutte HJ (1995) Urokinase plasminogen activator induces angiogenesis and tumor vessel invasion in breast cancer. Pathol Res Pract 191: 403-409.
  • Kaneko T, Konno H, Baba M, Tanaka T, Nakamura S (2003) Urokinase-type plasminogen activator expression correlates with tumor angiogenesis and poor outcome in gastric cancer. Cancer Sci 94: 43-49
  • Kim TD, Song KS, Li G, Choi H, Park HD, Lim K, Hwang BD, Yoon WH (2006) Activity and expression of urokinase-type plasminogen activator and matrix metalloproteinases in human colorectal cancer. BMC Cancer 6: 211.
  • Kohonen-Corish MR, Wang Y, Doe WF (1996) A highly polymorphic (CA)n repeat in intron 3 of the human urokinase receptor gene (PLAUR). Hum Genet 97: 124-125.
  • Kong D, Li Y, Wang Z, Banerjee S, Sarkar FH (2007) Inhibition of angiogenesis and invasion by 3,3'-diindolylmethane is mediated by the nuclear factor-kappaB downstream target genes MMP-9 and uPA that regulated bioavailability of vascular endothelial growth factor in prostate cancer. Cancer Res 67: 3310-3319.
  • Konno H, Abe J, Kaneko T, Baba M, Shoji A, Sunayama K, Kamiya K, Tanaka T, Suzuki S, Nakamura S, Urano T (2001) Urokinase receptor and vascular endothelial growth factor are synergistically associated with the liver metastasis of colorectal cancer. Jpn J Cancer Res 92: 516-523.
  • Kumar R, Kuniyasu H, Bucana CD, Wilson MR, Fidler IJ (1998) Spatial and temporal expression of angiogenic molecules during tumor growth and progression. Oncol Res 10: 301-311.
  • Mandriota SJ, Seghezzi G, Vassalli JD, Ferrara N, Wasi S, Mazzieri R, Mignatti P, Pepper MS (1995) Vascular endothelial growth factor increases urokinase receptor expression in vascular endothelial cells. J Biol Chem. 270: 9709-9716.
  • Min HY, Doyle LV, Vitt CR, Zandonella CL, Stratton-Thomas JR, Shuman MA, Rosenberg S (1996) Urokinase receptor antagonists inhibit angiogenesis and primary tumor growth in syngeneic mice. Cancer Res 56: 2428-2433.
  • Nagy JA, Brown LF, Senger DR, Lanir N, Van de Water L, Dvorak AM, Dvorak HF (1989) Pathogenesis of tumor stroma generation: a critical role for leaky blood vessels and fibrin deposition. Biochim Biophys Acta 948: 305-326.
  • Nielsen LS, Kellerman GM, Behrendt N, Picone R, Dano K, Blasi F (1988) A 55,000-60,000 Mr receptor protein for urokinase-type plasminogen activator. Identification in human tumor cell lines and partial purification. J Biol Chem 263: 2358-2363.
  • Pang RW, Poon RT (2006) Clinical implications of angiogenesis in cancers. Vasc Health Risk Manag 2: 97-108.
  • Pepper MS (2001) Role of the matrix metalloproteinases and plasminogen activator-plasmin systems in angiogenesis. Arterioscler Thromb Vasc Biol 21: 1104-1117.
  • Ploug M, Kjalke M, Ronne E, Weidle U, Hoyer-Hansen G, Dano K (1993) Localisation of the disulfide bond in the NH_2-terminal domain of the cellular receptor for human urokinase-type plasminogen activator: a domain structure belonging to a novel superfamily of glycolipid-anchored membrane proteins. J Biol Chem 268: 17539-17546.
  • Przybyłowska K, Smolarczyk K, Błasiak J, Kulig A, Romanowicz-Makowska H, Dziki A, Ulańska J, Pander B (2001) A C/T polymorphism in the urokinase-type plasminogen activator gene in colorectal cancer. J Exp Clin Cancer Res 20: 569-572.
  • Przybylowska K, Smolarczyk K, Kulig A, Romanowicz-Makowska H, Dziki A, Ulanska J, Pander B, Blasiak J (2002) Antigen levels of the urokinase-type plasminogen activator and its gene polymorphisms in colorectal cancer. Cancer Lett 181: 23-30.
  • Rajaganeshan R, Prasad R, Guillou PJ, Chalmers CR, Scott N, Sarkar R, Poston G, Jayne DG (2007) The influence of invasive growth pattern and microvessel density on prognosis in colorectal cancer and colorectal liver metastases. Br J Cancer 96: 1112-1117.
  • Reijerkerk A, Mosnier LO, Kranenburg O, Bouma BN, Carmeliet P, Drixler T, Meijers JC, Voest EE, Gebbink MF (2003). Amyloid endostatin induces endothelial cell detachment by stimulation of the plasminogen activation system. Mol Cancer Res 1: 561-568.
  • Reuning K, Ulm H, Hofler F, Janicke H, Graeff AB (1997) Clinical impact of the plasminogen activation system in tumor invasion and metastasis: prognostic relevance and target for therapy. Thromb Haemost 78: 285-296.
  • Seetoo DQ, Crowe PJ, Russell PJ, Yang JL (2003) Quantitative expression of protein markers of plasminogen activation system in prognosis of colorectal cancer. J Surg Oncol 82: 184-193.
  • Shpitz B, Gochberg S, Neufeld D, Grankin M, Buklan G, Klein E, Bernheim J (2003) Angiogenic switch in earliest stages of human colonic tumorigenesis. Anticancer Res 23: 5153-5157.
  • Sieczkiewicz GJ, Hussain M, Kohn EC (2002) Angiogenesis and metastasis. Cancer Treat Res 107: 353-381.
  • Smolarz B, Romanowicz-Makowska H, Kulig A (2003) Plasminogen activator inhibitor 1 (PAI-1) 1334G/A genetic polymorphism in colorectal cancer. Acta Biochim Polon 50: 489-495.
  • Wang Y, Jones CJ, Dang J, Liang X, Olsen JE, Doe WF (1994) Human urokinase receptor expression is inhibited by amiloride and induced by tumor necrosis factor and phorbol ester in colon cancer cells. FEBS Lett 353: 138-142.
  • Zheng H, Takahashi H, Murai Y, Cui Z, Nomoto K, Niwa H, Tsuneyama K, Takano Y (2006) Expressions of MMP-2, MMP-9 and VEGF are closely linked to growth, invasion, metastasis and angiogenesis of gastric carcinoma. Anticancer Res 26: 3579-3583.
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