| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Research Abstract |
It has been reported that platelets could help the formation of hematogenous metastasis in many cancers. However, the mechanism is not completely elucidated. Recently, IL-8, released by some cancer cells, has been considered to be one of important caytokines to promote angiogenesis as well as cancer invasion and proliferation. In the present study, we have shown that platelets could become activated after the co-incubation with human pancreatic adenocarcinoma cells MIA PaCa-2 and enhanced IL-8 release by cancer cells in the platelet number dependent manner. Northern blot analysis revealed that the expression of IL-8 mRNA by MIA PaCa-2 was also strongly upregulated in the presence of platelets. The co-incubation of tumor cells with the supernatant from thrombin-activated platelets resulted in a slight enhancement of IL-8 release. However, remaining degranulated platelets caused much greater enhancement in IL-8 production. Furthermore, MIA PaCa-2 cells cultured with platelets in the same chamber induced much more production of IL-8 than those cultured with platelets prevented from direct contact by a membrane barrier in the double chamber culture well study. In addition, fixed, thrombin-activated platelets significantly enhanced IL-8 release by MIA PaCa-2 cells, although fixed, unstimulated-platelets did not enhance the production of IL-8. Finally, all of pancreatic cancer cells tested here adhered to at least one platelet on their surface at 70 to 90%, and adhered to three or more platelets at 30 to 50%. These findings suggest that platelets could be involved in the tumor progression by the direct cantact to tumor cells as well as soluble factors derived from activated platelets through the enhancement of IL-8 release by tumor cells.
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