Failure Of Mmp-9 Dimer Induction By Pma In Normal Human Cell Lines

In a previous study we found that MMP-9 dimer secretion patterns of cancer cells fell into different categories and that high MMP-9 and dimer secretion levels correlated with the most aggressive cancer cell lines. Cytokines and signal transduction pathways, including those activated by phorbol 12-myristate 13-acetate (PMA), regulate the expression of MMPs. The aim of this study was to examine the pattern of MMP-2, MMP-9 and MMP-9 dimer expression in human normal cells from various tissues treated with PMA.  Epithelial, connective, and muscle tissues were selected since carcinomas, sarcomas, and adenosarcomas are derived from these tissue types, respectively. The cell lines were cultured in their recommended media and supplemented with 10% FBS and antibiotics in 24-well tissue culture plates. At near confluence, the cells were washed and fresh medium added. A parallel set of cultures was treated with PMA. After 24h incubation, media were collected and analyzed for MMP-2, MMP-9 monomer and dimer by gelatinase zymography. The results indicated that cell expression of MMP-2 and MMP-9 depended on their primary tissue subtype. All cell lines, regardless of tissue origin, expressed MMP-2. PMA induced MMP-9 expression in glandular epithelia, supportive connective tissue, and muscle tissue cell lines. However, cell lines of endothelial origin and proper connective tissue were insensitive to PMA.  We observed no MMP-9 dimer secretion in any of the cell lines tested, which implies that cell migration is not supported by these cells

Running title: Normal cell absence of MMP-9 dimers
Keywords: MMP-9 dimers, normal human cell lines, PMA


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