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Platelet-Activating Factor Enhances Experimental Pulmonary Metastasis of Murine Sarcoma Cells by Up-regulation of Matrix Metalloproteinases-9 Through NF-$kappa$B-Dependent Pathway
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  • Platelet-Activating Factor Enhances Experimental Pulmonary Metastasis of Murine Sarcoma Cells by Up-regulation of Matrix Metalloproteinases-9 Through NF-$kappa$B-Dependent Pathway
  • Platelet-Activating Factor Enhances Experimental Pulmonary Metastasis of Murine Sarcoma Cells by Up-regulation of Matrix Metalloproteinases-9 Through NF-$kappa$B-Dependent Pathway
저자명
Ko. Hyun-Mi,Back. Hae-Kyong
간행물명
Journal of experimental & biomedical sciences
권/호정보
2004년|10권 2호|pp.143-151 (9 pages)
발행정보
대한의생명과학회
파일정보
정기간행물|ENG|
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이 논문은 한국과학기술정보연구원과 논문 연계를 통해 무료로 제공되는 원문입니다.
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기타언어초록

Matrix metalloproteinases (MMPs) are capable of degrading extracellular matrix, a process that is necessary for angiogenesis, tumor invasion and metastasis. Platelet-activating factor (PAP) increases angiogenesis, tumor growth and metastasis through nuclear factor (NF)-$kappa$B activation. Based on these facts, the involvement of MMPs in PAF-induced pulmonary metastasis was investigated in murine sarcoma cells, MMSV-BALB/3T3. Messenger RNA expression and enzymatic activity of MMP-9 were assessed by RT-PCR and zymography, and cell migration and metastasis were done for the detection of MMP-9 functional activity. PAP induced mRNA expression and enzymatic activity of MMP-9, and its effects were either inhibited by the PAP antagonist, WEB 2170 or by the NF-$kappa$B inhibitor, parthenolide, or p65 antisense oligonucleotide in a dose-dependent manner. In addition, PAF induced promoter activity of MMP-9, which was inhibited by WEB 2170, phenanthroline, NAC, PDTC. These results indicate that PAF induces mRNA expression and enzymatic activity of MMP-9 in NF-$kappa$B dependent manner. Cell migration assay showed that PAF induced MMSV-BALB/3T3 migration, and its effect was significantly inhibited by treatment with phenanthroline. PAF enhanced pulmonary metastasis of murine sarcoma cells, MMSV-BALB/3T3 was also reduced by phenanthroline. These results suggest that PAF-enhanced cell migration and pulmonary metastasis is mediated through the expression of MMP. In conclusion, It is suggested that PAF enhances pulmonary metastasis by inducing MMP-9 expression via the activation of NF-$kappa$B.