Analysis of the mechanism of apperance of the autocrine motility factor in rheumatoid arthritis

2001 Fiscal Year Final Research Report Summary

• Project/Area Number: 12671394
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Orthopaedic surgery
• Research Institution: Gunma University
• Principal Investigator: TAKEUCHI Kimihiko Gunma University School of Medicine Assistant, 医学部, 助手 (20302466)
• Co-Investigator(Kenkyū-buntansha): TAKAGISHI Kenji Gunma University of Medicine Professor, 医学部, 教授 (70154763) ; WATANABE Hideomi Gunma University of Medicine Lecturer, 医学部, 講師 (40231724)
• Project Period (FY): 2000 – 2001
• Keywords: rheumatoid arthritis / AMF / PHI / FDG-PET / glycolysis / synovial fluid / gp78 / anti-gp78

Research Abstract

The autocrine motility factor (AMF) which tumor secreted as a cytokine stimulates cell migration in vivo and metastasis in vitro. We identified cell motile activity not only in synovial fluid but also in serum of patients with rheumatoid arthritis (RA). Because the biochemical features of this activity were same as that of AMF, we confirm this activity to be AMF. AMF was isolated, purified, and microsequenced. And the results demonstrated that AMF is the previously cloned enzyme designed as Neuroleukin, and Phosphohexose isomerase (PHI), which has been independently implicated in cell motility, and to be a cancer progression marker. PHI catalyzes isomerization of glucose 6-phosphate to fructose 6-phosphate and specific for both sugars. Because PHI is a key enzyme of glycolytic metabolism related to accumulation of FDG within tissue, it plays an important role at a site where has an active glucose metabolism in tumor cells, or inflammatory cells. The glucose analogue, FDG, is widely used to evaluate various tumors with FDG-PET imaging. The standardized uptake value (SUV) calculated with FDG can be used as a quantitative marker of inflammation. The Lansbury index, which indicates disease activity of RA, has efficient correlation with FDG-SUV value. Serum CRP value and the number of platelet have also efficient correlation with FDG-SUV value. Histopathological examination shows that FDG-SUV value is high as the degree of neovasculization.
Because synoviocytes and other inflammatory cells proliferate in rheumatoid synovial joints, AMF is considered to make a great contribution in the site of active inflammation.