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


CONCLUSIONS
We conclude that activated MMP-2 and MMP-1 are important in the invasive activity of these ovarian cancer cells.
Nishikawa
A
A
Department of Obstetrics and Gynecology, School of Medicine, Sapporo Medical University, S1 W16, Chuo-ku, Sapporo, 060-8543, Japan. anisikaw@sapmed.ac.jp
Iwasaki
M
M
Akutagawa
N
N
Manase
K
K
Yamashita
S
S
Endo
T
T
Kudo
R
R
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017500:Adenovirus E1A Proteins / Q000096:biosynthesis* / Q000235:genetics; D018269:Carcinoma, Endometrioid / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D002455:Cell Division / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D020782:Matrix Metalloproteinases / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010051:Ovarian Neoplasms / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology*; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis / Q000235:genetics; D017396:Plasminogen Activator Inhibitor 2 / Q000096:biosynthesis / Q000235:genetics; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis / Q000235:genetics; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism
D017500:Adenovirus E1A Proteins; C494041:ETS1 protein, human; C079853:ETV4 protein, human; D004792:Enzyme Precursors; D017395:Plasminogen Activator Inhibitor 1; D017396:Plasminogen Activator Inhibitor 2; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D014157:Transcription Factors; D019716:Tissue Inhibitor of Metalloproteinase-2; D014568:Urokinase-Type Plasminogen Activator; D020782:Matrix Metalloproteinases