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      Influence of cytokines and growth factors on matrix metalloproteinase-2 production and invasion of human renal cancer.

      Urological Research
      Cytokines, pharmacology, Gelatinases, biosynthesis, genetics, Growth Substances, Humans, Kidney Neoplasms, metabolism, pathology, Matrix Metalloproteinase 2, Metalloendopeptidases, Neoplasm Invasiveness, RNA, Messenger, Tumor Cells, Cultured

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          Abstract

          This study evaluated the influence of cytokines and growth factors on the production of matrix metalloproteinase-2 (MMP-2, 72-kDa type IV collagenase, gelatinase A) and invasion of the human renal cell carcinoma (HRCC) cell line KG-2. The cells were treated with cytokines and growth factors, and the gelatiolytic activity and in vitro invasion were examined. Basic fibroblast growth factor (bFGF) stimulated MMP-2 production by KG-2 cells to 2.0-, 4.84- and 4.53-fold that of the untreated group at 0.1, 1.0 and 10 ng/ml, respectively. Transforming growth factor-beta1 (TGF-beta1) at very low concentrations of 10 pg/ml and 100 pg/ml stimulated enzyme production in KG-2 cells by 1.74- and 2.83-fold, respectively. In contrast, interferon-gamma (IFN-gamma) decreased MMP-2 production by KG-2 cells at 10 and 100 U/ml to 69% and 41% of the level in the untreated group, respectively. At those concentrations, IFN-gamma did not cause cytostasis in KG-2 cells. Moreover, bFGF and TGF-beta1 (low concentrations) stimulated in vitro invasion of KG-2 cells, but IFN-gamma decreased the invasive activity, which was well correlated with the levels of MMP-2. However, the expression of MMP-2 mRNA of KG-2 cells treated with 10 ng/ml bFGF, 100 pg/ml TGF-beta1 and 100 U/ml IFN-gamma was shown to be 3.8-, 3.4- and 0.7-fold, respectively, those in untreated groups. Thus the production of MMP-2 in HRCC was influenced by cytokines and growth factors, and MMP-2 plays an important role in the invasion and metastasis of certain types of HRCC.

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