| Co-Investigator(Kenkyū-buntansha) |
UCHIDA Shinji KURUME UNIVERSITY SCHOOL OF MEDICINE.M.D, 医学部, 助手 (00248428)
NAKAMURA Yukiyasu KURUME UNIVERSITY SCHOOL OF MEDICINE.M.D, 医学部, 助手 (60227949)
KIMITSUKI Hiroshi KURUME UNIVERSITY SCHOOL OF MEDICINE.M.D, 医学部, 助手 (10195349)
KUROHIJI Toshihiko KURUME UNIVERSITY SCHOOL OF MEDICINE.M.D, 医学部, 助手 (00178146)
柳瀬 豊 久留米大学, 医学部, 助手 (10230278)
立石 勉 久留米大学, 医学部, 助手 (60248416)
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| Budget Amount *help |
¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1995: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1994: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Research Abstract |
1 The localization of thrombospondin (TSP) in hepatocellular carcinoma (HCC) was investigated by light and electron microscopic immunohistochemical studies. Tissue specimens were obtained by surgical resection from sixty patients with HCC.In light microscopic immunohistochemistry, all specimens showed strong TSP expression in fibrous tissues in HCC and surrounding non-malignant areas. In 31 of 60 cases, TSP expression was observed in HCC cells. In electron microscopic immunohistochemistry, TSP was localized in the rough endoplasmic reticulum (RER) of HCC cells, and also in the RER of fibroblasts and endothelial cells. These findings proved that TSP was synthesized in HCC cells, in endothelial cells, in fibroblasts surrounding the tumor, and further suggested that TSP in the fibrous tissues surrounding carcinoma was basically synthesized by nonparenchymal cells such as fibroblasts and endothelial cells.
2 To explore the role of TSP of HCC we measured blood TSP levels by indirect ELISA fr
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om 30 control subjects and 30 patients with HCC.In HCC patients, elevated levels of TSP greater than the mean value for controls ranging were found. Moreover, in intrahepatic metastasis of HCC,TSP levels were greater than nonmetastasis. These results suggested that TSP may play a role in metastasis of HCC and could serve as a blood marker for metastasis.
3. In light microscopic and electron microscopic immunohistochemistry, HCC cells showed TSP and its receptor expression. Addition of anti-TSP antibody to cultured medium showed marked suppression of cell proliferation in HCC cells. On the other hand, addition of TSP to culture medium stimulated cell proliferation, in KYN-2 and KYN-3. Furthermore, the effect of anti-TSP antibody induced growth arrest in the G_0G_1 phase of the cell cycle and decreased DNA synthesis on HuH-7 cell. Addition of anti-CSVTCG receptor antibody to cultured medium showed marked suppression of cell proliferation. In conclusion, TSP promoted the proliferation of HCC cells. Less
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