Essential roles of tumor necrosis factor receptor p55 in liver metastasis of intrasplenic administration of colon 26 cells.
Intrasplenic administration of a colon adenocarcinoma cell line, colon 26, induced tumor necrosis factor (TNF) alpha protein expression around the central and portal veins of the liver at 3 days, and liver metastases by 24 days after the tumor injection, in 90% of wild-type (WT) mice. To explore the roles of TNF-alpha in the process, we administered colon 26 cells into tumor necrosis factor receptor p55 (TNF-Rp55) knockout (KO) mice. Less than 50% of TNF-Rp55 KO mice developed liver metastasis with significantly lower liver weights and the volumes of metastatic foci. These observations suggest the critical roles of TNF-Rp55-mediated signals in this liver metastasis model. The intrasplenic tumor injection induced mRNA expressions of vascular endothelial growth factor, heparin-binding epidermal growth factor, matrix metalloproteinase-9, and tissue inhibitor of matrix metalloproteinase-1 at similar levels in the livers of both WT and TNF-Rp55 KO mice. Immunohistochemical analyses of the livers of WT mice after tumor injection demonstrated the enhanced expression of vascular cell adhesion molecule (VCAM)-1 and E-selectin on sinusoidal endothelial cells. Enhanced E-selectin expression was similarly observed in the liver of TNF-Rp55 KO mice after tumor injection. However, the enhancement in VCAM-1 mRNA expression and its protein production was significantly attenuated in the liver of TNF-Rp55 KO mice when compared with WT mice. Collectively, these observations suggest that TNF-Rp55-mediated signals can up-regulate both VCAM-1 expression in the liver and subsequent liver metastasis after intrasplenic tumor injection.
Kitakata
Hidekazu
H
Division of Molecular Bioregulation, Kanazawa University, Kanazawa 920-0934, Japan.
Nemoto-Sasaki
Yoko
Y
Takahashi
Yutaka
Y
Kondo
Toshikazu
T
Mai
Masayoshi
M
Mukaida
Naofumi
N
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000556:secondary*; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000502:physiology*; D003110:Colonic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D005260:Female; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008114:Liver Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism / Q000556:secondary*; D020782:Matrix Metalloproteinases / Q000096:biosynthesis; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D009368:Neoplasm Transplantation; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor / Q000235:genetics / Q000502:physiology*; D047888:Receptors, Tumor Necrosis Factor, Type I; D015398:Signal Transduction / Q000502:physiology; D013154:Spleen / Q000473:pathology; D019714:Tissue Inhibitor of Metalloproteinases / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000502:physiology; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis
D015703:Antigens, CD; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D019714:Tissue Inhibitor of Metalloproteinases; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; D020782:Matrix Metalloproteinases