Plasminogen fragmentation and increased production of extracellular matrix-degrading proteinases are associated with serous epithelial ovarian cancer progression

Padma Murthi*, Gillian Barker, Cameron J. Nowell, Gregory E. Rice, Mark S. Baker, Bill Kalionis, Michael A. Quinn

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Citations (Scopus)

Abstract

Objective. Elevated levels of proteases are linked to the malignant phenotype in a wide variety of solid tumors. Therefore, the expression of plasminogen, matrix metalloproteinases (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 (n = 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, semiquantitative estimates of MMP-2, MMP-9, total MMP 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. MMP 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.

Original languageEnglish
Pages (from-to)80-88
Number of pages9
JournalGynecologic Oncology
Volume92
Issue number1
DOIs
Publication statusPublished - Jan 2004

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