Essential roles of tumor necrosis factor receptor p55 in liver metastasis of intrasplenic administration of colon 26 cells.

Abstract

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.

• Authors: Hidekazu Kitakata, Yoko Nemoto-Sasaki, Yutaka Takahashi, Toshikazu Kondo, Masayoshi Mai, Naofumi Mukaida
• Journal: Cancer research (Cancer Res) Vol. 62 Issue 22 Pg. 6682-7 (Nov 15 2002) ISSN: 0008-5472 [Print] United States
• PMID: 12438267 (Publication Type: Journal Article)

Chemical References

• Antigens, CD
• RNA, Messenger
• Receptors, Tumor Necrosis Factor
• Receptors, Tumor Necrosis Factor, Type I
• Tissue Inhibitor of Metalloproteinases
• Tumor Necrosis Factor-alpha
• Vascular Cell Adhesion Molecule-1
• Matrix Metalloproteinases

Topics

• Adenocarcinoma (genetics, metabolism, pathology, secondary)
• Animals
• Antigens, CD (genetics, physiology)
• Colonic Neoplasms (genetics, metabolism, pathology)
• Female
• Liver (metabolism, pathology)
• Liver Neoplasms, Experimental (genetics, metabolism, secondary)
• Matrix Metalloproteinases (biosynthesis)
• Mice
• Mice, Inbred BALB C
• Mice, Knockout
• Neoplasm Transplantation
• RNA, Messenger (biosynthesis, genetics)
• Receptors, Tumor Necrosis Factor (genetics, physiology)
• Receptors, Tumor Necrosis Factor, Type I
• Signal Transduction (physiology)
• Spleen (pathology)
• Tissue Inhibitor of Metalloproteinases (biosynthesis)
• Tumor Necrosis Factor-alpha (biosynthesis, physiology)
• Vascular Cell Adhesion Molecule-1 (biosynthesis)