Expression of various matrix proteases and Ets family transcriptional factors in ovarian cancer cell lines: correlation to invasive potential

Gynecol Oncol. 2000 Nov;79(2):256-63. doi: 10.1006/gyno.2000.5944.


Objectives: The aim of our study was to determine the important molecules responsible for the invasive activity of ovarian cancer cells.

Methods: We compared the biological characteristics, that is, growth rate, motility, and invasive activity, of five ovarian cancer cell lines with the gene expression of various matrix proteases (matrix metalloproteinase-1 [MMP-1], MMP-2, MMP-9, membrane-type MMP type 1 [MT1-MMP], MT2-MMP, MT3-MMP, urokinase plasminogen activator [uPA]), their inhibitors (tissue inhibitor of metalloproteinase type 1 [TIMP-1], TIMP-2, plasminogen activator inhibitor type 1, [PAI-1], and PAI-2), and the potential transcriptional regulators E1AF and Ets-1.

Results: There was no clear correlation in the growth rate, motility, and invasion, suggesting that there are independent properties for malignant potential in ovarian cancer cells. However, HTBOA, a poorly differentiated cancer cell line, exhibited highly invasive activity, rapid growth, and increased motility. This cell line also expressed both Ets transcriptional factors, E1AF and Ets-1, and many matrix-degrading enzymes. Three cell lines that expressed E1AF showed rapid cell growth. The highly invasive cell lines, HTBOA and HTOA (well-differentiated serous cystadenocarcinoma), produced either MMP-2 or MMP-1, and both cell lines expressed MT1-MMP and uPA. Furthermore, the active forms of pro-MMP-2 and pro-MMP-1 were detected in HTBOA and HTOA by zymography.

Conclusion: We conclude that activated MMP-2 and MMP-1 are important in the invasive activity of these ovarian cancer cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology
  • Adenovirus E1A Proteins / biosynthesis*
  • Adenovirus E1A Proteins / genetics
  • Carcinoma, Endometrioid / enzymology
  • Carcinoma, Endometrioid / genetics
  • Carcinoma, Endometrioid / pathology
  • Cell Division / physiology
  • Cell Movement / physiology
  • Cystadenocarcinoma, Serous / genetics
  • Cystadenocarcinoma, Serous / metabolism
  • Cystadenocarcinoma, Serous / pathology
  • Enzyme Activation
  • Enzyme Precursors / metabolism
  • Female
  • Gene Expression
  • Humans
  • Matrix Metalloproteinases / biosynthesis*
  • Matrix Metalloproteinases / genetics
  • Matrix Metalloproteinases / metabolism
  • Neoplasm Invasiveness
  • Ovarian Neoplasms / enzymology
  • Ovarian Neoplasms / metabolism*
  • Ovarian Neoplasms / pathology*
  • Plasminogen Activator Inhibitor 1 / biosynthesis
  • Plasminogen Activator Inhibitor 1 / genetics
  • Plasminogen Activator Inhibitor 2 / biosynthesis
  • Plasminogen Activator Inhibitor 2 / genetics
  • Proto-Oncogene Protein c-ets-1
  • Proto-Oncogene Proteins / biosynthesis*
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins c-ets
  • RNA, Messenger / biosynthesis
  • RNA, Messenger / genetics
  • Tissue Inhibitor of Metalloproteinase-1 / biosynthesis
  • Tissue Inhibitor of Metalloproteinase-1 / genetics
  • Tissue Inhibitor of Metalloproteinase-2 / biosynthesis
  • Tissue Inhibitor of Metalloproteinase-2 / genetics
  • Transcription Factors / biosynthesis*
  • Transcription Factors / genetics
  • Tumor Cells, Cultured
  • Urokinase-Type Plasminogen Activator / biosynthesis*
  • Urokinase-Type Plasminogen Activator / genetics
  • Urokinase-Type Plasminogen Activator / metabolism


  • Adenovirus E1A Proteins
  • ETS1 protein, human
  • ETV4 protein, human
  • Enzyme Precursors
  • Plasminogen Activator Inhibitor 1
  • Plasminogen Activator Inhibitor 2
  • Proto-Oncogene Protein c-ets-1
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-ets
  • RNA, Messenger
  • Tissue Inhibitor of Metalloproteinase-1
  • Transcription Factors
  • Tissue Inhibitor of Metalloproteinase-2
  • Urokinase-Type Plasminogen Activator
  • Matrix Metalloproteinases