| Co-Investigator(Kenkyū-buntansha) |
KAWANO Sunao Osaka University, Graduate Sch.of Med.and Clin.Lab.Sci.Sch.of alli.Health, Prof., 医学系研究科, 教授 (60133138)
TSUJI Shingo Osaka University, Graduate Sch.of Med.Dept.of Int.Med.and Ther., Associate Prof., 医学系研究科, 講師 (40301262)
|
|---|
| Research Abstract |
Recent advances in surgical treatment have improved the prognosis of CRC, but the most critical determinant of mortality is distant spread of disease at the time of diagnosis. Therefore, it is important to develop more effective prevention measures to avoid the onset of metastasis. The mortality rates from colon cancer patients who are taking nonsteroidal anti-inflammatory drugs are significantly low compared with those who are not taking these drugs. Cyclooxygenase (COX) is a major target of NSAIDs and the inducible COX, COX-2, is upregulated in gastrointestinal cancers. Several epidemiological reports suggested that COX-2 expression has an important role in hematogenous metastasis of colon cancer. In the present study, we investigated the interaction between COX-2 activity and metastatic potential
Effects of COX-2 activity and prostaglandin E2 on tumor cell adhesion to endothelial cells, expression of sialyl Lewis antigens, and glycosyltransferase genes were determined in Caco-2 cells, a colon cancer cell line with low COX-2 expression, and Caco-2-COX-2, Caco-2 cells programmed to overexpress COX-2. Caco-2-COX-2 had increased Span-1 levels and increased adherence to endothelial cells via Span-1 compared with Caco-2. Treatment with COX-2 inhibitors decreased Span-1 expression and adherence to endothelial cells. B3Gal-T5 and ST3Gal III and IV expression were enhanced in Caco-2-COX-2 or PGE2-treated Caco-2. COX-2 inhibitors inhibited these expressions in Caco-2-COX-2. In intra-splenic injection, a model of liver metastasis, Caco-2-COX-2 metastasized to the liver, whereas Caco-2 did not. Pretreatment with COX-2 inhibitors reduced the metastatic potential
These results indicate a direct link between COX-2 and enhanced adhesion of carcinoma cells to endothelial cells, and enhanced liver metastatic potential via accelerated production of sialyl Lewis antigens. COX-2 inhibitors may suppress metastasis
|
