Plasminogen fragmentation and increased production of extracellular matrix-degrading proteinases are associated with serous epithelial ovarian cancer progression
Plasminogen fragmentation and increased production of extracellular matrix-degrading proteinases are associated with serous epithelial ovarian cancer progression
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DOI：
10.1016/j.ygyno.2003.09.016
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发表时间：
2004-01-01
影响因子：
4.7
通讯作者：
Quinn, MA
中科院分区：
文献类型：
--
作者：
Murthi, P;Barker, G;Quinn, MA
Objective. Elevated levels of proteases are linked to the malignant phenotype in a wide variety of solid tumors. Therefore, the expression of plasminogen, matrix metalloprotemases (MMP-2 and MMP-9), and of the serine protease urokinase-type plasminogen activator (uPA) in serous epithelial carcinoma of the ovary were investigated.Methods. Plasminogen antigen was analyzed in tissue extracts and in the urine of patients with normal (n = 12), benign (17 = 6), borderline (n = 9), and invasive serous tumors (n = 22) by Western immunoblotting using rabbit polyclonal plasminogen and murine monoclonal angiostatin antibodies. In the same tissue extracts, semi quantitative estimates of MMP-2, MMP-9, total MNIP activity, and uPA activity were determined using semiquantitative gelatin zymography in the presence or absence of human plasminogen.Results. Bands corresponding to Glu-plasminogen (approximately 92 kDa) and Lys-plasminogen (approximately 86 kDa) were detected in all ovarian tissues and in corresponding urine samples. Densitometric analysis of combined Glu- or Lys-plasminogen levels showed significantly decreased levels in malignant compared to normal tissue. In Grade 3 cancers, there was no evidence of Glu-plasminogen or angiostatin. NIMP activity was significantly elevated in both borderline and in Grade 3 ovarian cancer tissues. Increased tissue uPA activity on zymograms was detected only in Grade 3 ovarian cancer tissue.Conclusion. These data suggest that proteolytic activity of the plasminogen activation cascade increases in serous epithelial ovarian carcinoma. (C) 2003 Elsevier Inc. All rights reserved.
