Critical role for matrix metalloproteinase‐9 in platelet‐activating factor‐induced experimental tumor metastasis

• Published in: International journal of cancer Vol. 120; no. 6; pp. 1277 - 1283
• Main Authors: Ko, Hyun‐Mi, Kang, Jee‐Hae, Jung, Bongnam, Kim, Han‐A, Park, Sung Jun, Kim, Kyoung‐Jin, Kang, Yeong‐Rim, Lee, Hern‐Ku, Im, Suhn‐Young
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15-03-2007; Wiley-Liss
• Subjects: Animal tumors. Experimental tumors; Animals; AP‐1; Biological and medical sciences; Experimental respiratory system tumors; Lung Neoplasms - enzymology; Lung Neoplasms - secondary; Matrix Metalloproteinase 2 - analysis; Matrix Metalloproteinase 2 - physiology; Matrix Metalloproteinase 9 - analysis; Matrix Metalloproteinase 9 - physiology; Matrix Metalloproteinase Inhibitors; matrix metallproteinases; Medical sciences; Melanoma, Experimental - chemically induced; Melanoma, Experimental - enzymology; Melanoma, Experimental - secondary; metastasis; Mice; Mice, Inbred C57BL; Neoplasm Metastasis; NF-kappa B - antagonists & inhibitors; NF‐κB; Platelet Activating Factor - pharmacology; Platelet Activating Factor - toxicity; platelet‐activating factor; Skin Neoplasms - chemically induced; Skin Neoplasms - enzymology; Skin Neoplasms - pathology; Transcription Factor AP-1 - antagonists & inhibitors; Tumors; Metalloendopeptidases; platelet-activating factor; AP-1; Signal transduction; Cancerology; metastasis; Established cell line; Malignant melanoma; Extracellular matrix; Transcription factor NFκB; Lung disease; Respiratory disease; Enzyme; Rodentia; NF-KB; Malignant tumor; Platelet activating factor; Gelatinase B; Peptidases; Vertebrata; Mammalia; Mouse; Lung metastasis; Animal; matrix metallproteinases; Hydrolases; Experimental tumor; Transcription factor AP1
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.22450

In this study, the roles of matrix metalloproteinase (MMP)‐2 and MMP‐9 in platelet‐activating factor (PAF)‐induced experimental pulmonary metastasis of the murine melanoma cell, B16F10, were investigated. An injection of PAF resulted in increases in mRNA expression, protein levels and the activities of both MMP‐2 and MMP‐9 in the lungs. The overall expression of MMP‐9 was stronger than that of MMP‐2. The increased MMP‐9 expression was inhibited by both NF‐κB and AP‐1 inhibitors, whereas the increased MMP‐2 expression was inhibited by only AP‐1 inhibitors. Immunohistochemical analysis revealed that MMP‐9 was expressed in bronchial epithelial cells as well as in the walls of blood vessels, whereas MMP‐2 expression was observed only in bronchial epithelial cells. PAF significantly enhanced the pulmonary metastasis of B16F10, which was inhibited by both NF‐κB and c‐jun inhibitors. MMP‐9 inhibitor, but not that of MMP‐2, completely inhibited PAF‐induced B16F10 metastasis. These data indicate that MMP‐9, the expression of which was regulated by NF‐κB and AP‐1, plays a critical role in PAF‐induced enhancement of pulmonary melanoma metastasis. © 2006 Wiley‐Liss, Inc.