|Budget Amount *help
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥3,000,000 (Direct Cost: ¥3,000,000)
The various invasive and metastatic genes have the common transcriptional factors such as AP-1, AP-2, SP-1 or NF-Kappa B.In our study, We investigated the relationship between these transcriptional activities and the abilities of invasion and metastasis. In this study, we used our SQUU cell lines derived from human oral squamous cell carcinoma. (When transplanted orthotopically, SQUU-A exhibited an expansive growth without either intravasation or cervical lymph nodemetastasis (0/13), while SQUU-B invaded the muscle with intravasation and cervical lymph node metastasis (86.7%, 13/15).).
Although In vitro migration assay showed the differences in the invasive ability between both unstimulated cell lines. In these cell lines, the transcriptional activities of AP-1, AP-2, SP-1 were detected, while that of NF-Kappa B was not. We stimulated these cell lines by growth factors (TNF-α, HGF, TGF-α, TGF-β, bFGF) and cytokines (IL-1 α, IL-1 β, IL-8, IL-12), respectively. TGF-α gave these cell lines
the highest ability of invasion among the growth factors and cytokines. That of non metastatic cell line was 0.93%, while that of metastatic cell line was 48.4%. The metastatic cell line got much higher ability of invasion. Interestingly, in the metastatic cell line, the transcriptional activity of AP-1, Which regulates matrix metaloproteinase (MMP), increased by various growth factors and cytokines. In addition, the active type of MMP-2 was detected in the metastatic cell lines by stimulation, while not in non metastatic cell line. By TGF-β, the metastatic cell line had the up-regulation of MMP-2 and the transcriptional activity of AP-2 which regulates MMP-2. That suggests that the increase of transcriptional activity of AP-1or AP-2 may result in the up-regulation of MMP and active MMP, and may cause the acquisition of invasive ability in the metastatic cell line. But this is the insufficient explanation about the mechanism of invasion, because both cell lines had the transcriptional activities of AP-1 and AP-2, and the different invasive ability even by unstimulation. TNF-α, IL-1α, IL-1β made both cell lines increase of MMP-9 and caused the transcriptional activity of NF-Kappa B.There were no differences between both cell lines. Therefore, we are necessarily investigating another transcriptional factors. Less