Expression of matrix metalloproteinase, tissue inhibitors of metalloproteinase and adhesion molecules in silicotic mice with lung tumor metastasis.
The number of metastatic foci in silicotic mice is approximately 1.5-fold that in normal mice and in mice treated with TiO2 as inert particles. Expression of matrix metalloproteinases (MMPs) tissue inhibitors of metalloproteinases (TIMPs) and selectins was investigated in silicotic mice with lung tumor metastasis. Expression of MMP-9 and P-selectin mRNA, but not MMP-2 and E-selectin, increased significantly, showing decreases of the ratio of expression in TIMPs/MMP-9 in tumor-bearing silicotic mice compared with the tumor-bearing normal mice and mice treated with TiO2. Pretreatment with anti-P-selectin antibody inhibited number of metastatic foci significantly in silicotic mice, while pretreatment of animals with anti MMP-9 antibody showed slight decrease of metastatic foci. This evidence indicated that up-regulation of P-selectin expression contributed to enhanced rate of tumor metastasis in lung with silicosis.
Ishihara
Yoko
Y
Department of Hygiene and Public Health (I), School of Medicine, Tokyo Womens Medical University, Krawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan. isihara@research.twmu.ac.jp
Nishikawa
Toshio
T
Iijima
Hiroko
H
Matsunaga
Kenichi
K
D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000150:complications / Q000201:enzymology / Q000378:metabolism* / Q000556:secondary; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics; D019040:E-Selectin / Q000096:biosynthesis / Q000235:genetics; D006651:Histocytochemistry; D008175:Lung Neoplasms / Q000150:complications / Q000201:enzymology / Q000378:metabolism* / Q000556:secondary; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis / Q000235:genetics; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis / Q000235:genetics; D020782:Matrix Metalloproteinases / Q000096:biosynthesis* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D019007:P-Selectin / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012829:Silicosis / Q000150:complications / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D050857:Synaptotagmins; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis / Q000235:genetics; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000096:biosynthesis / Q000235:genetics; D019714:Tissue Inhibitor of Metalloproteinases / Q000096:biosynthesis* / Q000235:genetics; D014025:Titanium / Q000633:toxicity
D015815:Cell Adhesion Molecules; D019040:E-Selectin; D019007:P-Selectin; D012333:RNA, Messenger; C494285:Syt15 protein, mouse; D019715:Tissue Inhibitor of Metalloproteinase-1; D019714:Tissue Inhibitor of Metalloproteinases; D019716:Tissue Inhibitor of Metalloproteinase-2; D050857:Synaptotagmins; C009495:titanium dioxide; D014025:Titanium; D020782:Matrix Metalloproteinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9