Critical role for matrix metalloproteinase-9 in platelet-activating factor-induced experimental tumor metastasis.
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-kappaB 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-kappaB 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-kappaB and AP-1, plays a critical role in PAF-induced enhancement of pulmonary melanoma metastasis.
Ko
Hyun-Mi
HM
Department of Biological Sciences, College of Natural Sciences, Chonnam National University, Kwangju 500-757, Republic of Korea.
Kang
Jee-Hae
JH
Jung
Bongnam
B
Kim
Han-A
HA
Park
Sung Jun
SJ
Kim
Kyoung-Jin
KJ
Kang
Yeong-Rim
YR
Lee
Hern-Ku
HK
Im
Suhn-Young
SY
D000818:Animals; D008175:Lung Neoplasms / Q000201:enzymology / Q000556:secondary; D020778:Matrix Metalloproteinase 2 / Q000032:analysis / Q000502:physiology; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000502:physiology*; D061965:Matrix Metalloproteinase Inhibitors; D008546:Melanoma, Experimental / Q000139:chemically induced / Q000201:enzymology / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000037:antagonists & inhibitors; D009362:Neoplasm Metastasis; D010972:Platelet Activating Factor / Q000494:pharmacology / Q000633:toxicity*; D012878:Skin Neoplasms / Q000139:chemically induced / Q000201:enzymology / Q000473:pathology; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors
D061965:Matrix Metalloproteinase Inhibitors; D016328:NF-kappa B; D010972:Platelet Activating Factor; D018808:Transcription Factor AP-1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9