Distinct patterns of matrix metalloproteinase-2 and-9 expression in normal human cell lines
Distinct patterns of matrix metalloproteinase-2 and-9 expression in normal human cell lines
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DOI：
10.3892/or_00000290
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发表时间：
2009-03-01
期刊：
影响因子：
4.2
通讯作者：
Niedzwiecki, A.
中科院分区：
文献类型：
--
作者：
Roomi, M. W.;Monterrey, J. C.;Niedzwiecki, A.
恶性肿瘤细胞对周围组织的侵袭是一个由基质降解酶介导的复杂过程。在许多实体瘤中，基质细胞中MMP，尤其是MMP-2和MMP-9的表达高于肿瘤细胞，表明基质细胞是这些酶的主要来源。细胞因子和信号转导通路，包括由佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）激活的那些，调节MMPs的表达。本研究的目的是检查MMP-2和MMP-9在人正常细胞和PMA处理的细胞中的表达模式，以确定特定的表达模式是否与不同来源的组织相关。选择上皮、结缔和肌肉组织，因为癌、肉瘤和腺瘤分别来源于这些组织类型。将细胞系在其推荐的培养基中培养，并在24孔组织培养板中补充10%FBS和抗生素。在接近汇合时，洗涤细胞并加入新鲜培养基。用PMA处理一组平行培养物。孵育24小时后，收集培养基并通过明胶酶谱法分析MMP-2和MMP-9。结果表明，MMP-2和MMP-9的正常细胞表达取决于其原发组织亚型。所有细胞系，无论组织来源，表达MMP-2。PMA诱导MMP-9在腺上皮、支持结缔组织和肌肉组织细胞系中表达。然而，内皮源和适当的结缔组织细胞系对PMA不敏感。这些结果表明，MMP-2和MMP-9的差异调节和理解这可能开辟了途径，使用这些酶作为治疗的目标。
Invasion of surrounding tissues by malignant cells is a complex process mediated by the matrix degrading enzymes. In many solid tumors, the expression of MMPs, especially MMP-2 and MMP-9, is higher in stromal cells than in the tumor cells, suggesting stromal cells as the major source of these enzymes. Cytokines and signal transduction pathways, including those activated by phorbol 12-myristate 13-acetatc (PMA), regulate the expression of MMPs. The aim of this study was to examine the pattern of MMP-2 and MMP-9 expression in human normal cells and in PMA-treated cells to determine if specific patterns of expression were associated with tissues of different origin. 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 24 h of incubation, media were collected and analyzed for MMP-2 and MMP-9 by gelatinase zymography. The results indicate that the normal cell expression of MMP-2 and MMP-9 depends 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. These results suggest that MMP-2 and MMP-9 are differentially regulated and an understanding of this may open up avenues to use these enzymes as targets for therapy.