Functional Analysis of Galectin-9 and Purification of Galectin-9 Binding Molecules on Cell Surface

Galectin-9 的功能分析及细胞表面 Galectin-9 结合分子的纯化

• 批准号: 13470051
• 负责人: HIRASHIMA mitsuomi
• 金额: $ 9.22万
• 依托单位: Kagawa Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470051/
• 关键词: Galectin-9; Eosinophil; Immune Cell; Tumor cell; Galectin-binding Molecule; Chemotaxis; Cell Aggregation; Apoptosis

1. Galectin-9 (Gal-9) is a unique eosinophil activation factor differing from other identified chemoattractants (J Immunol, 2002), and the linker peptide is found not to be involved in its function (Glycobiology, 2002). IFN induced up-regulation of Gal-9 in endothelial cells and fibroblasts, and the expressed Gal-9 on their surface is associated with selective adhesion of eosinophils (J Leukocyte Biol, 2002; J Immunol, 2002). We also found that Gal-9 induces aggregation and apoptosis of tumor cells such as melanoma and breast cancer, and higher Gal-9 expression is linked to better prognosis of those patients (Int J Cancer, 2002; 25^<th> San Antonio Breast Cancer Symposium). Thus, immunohistochemical analysis can be used for determining the prognosis of tumor patients, especially in remote metastasis.2. Production and release of Ga-1-9 is induced by PMA in Jurkat T cell line, and an MMP is involved in the release (Glycobiology, 2002). We are continuing the study on the production and release of Gal-9 using mast cells and macrophages.3. Apoptosis induced by Gal-9 is suppressed by the presence of lactose indicating that Gal-9 binding molecules (glycoprotein with beta-galactoside) is present on the surface. We found that Gal-9 induces apoptosis through calcium-calpain-caspase pathway (J Immunol, 2003 in press). Now, we have purified the candidates of Gal-9 binding molecule involving in Ga-9-induced apoptosis, and clarifying which molecule is the Gal-9 binding molecule for the apoptosis.

1.半乳糖凝集素-9（Gal-9）是一种独特的嗜酸性粒细胞活化因子，不同于其他鉴定的化学引诱物（J Immunol，2002），并且发现接头肽不参与其功能（Glycobiology，2002）。IFN诱导内皮细胞和成纤维细胞中Gal-9的上调，并且在其表面上表达的Gal-9与嗜酸性粒细胞的选择性粘附相关（J Leukocyte Biol，2002; J Immunol，2002）。我们还发现Gal-9诱导肿瘤细胞如黑素瘤和乳腺癌的聚集和凋亡，并且更高的Gal-9表达与那些患者的更好预后相关（Int J Cancer，2002; 25^<th>圣安东尼奥乳腺癌研讨会）。因此，免疫组化分析可用于判断肿瘤患者的预后，尤其是远处转移. PMA在Jurkat T细胞系中诱导Ga-1-9的产生和释放，并且MMP参与释放（Glycobiology，2002）。我们正在继续利用肥大细胞和巨噬细胞研究Gal-9的产生和释放。乳糖的存在抑制了Gal-9诱导的细胞凋亡，表明表面上存在Gal-9结合分子（具有β-半乳糖苷的糖蛋白）。我们发现Gal-9通过钙-钙蛋白酶-半胱天冬酶途径诱导细胞凋亡（J Immunol，2003出版中）。目前，我们已经纯化了参与Ga-9诱导的细胞凋亡的Gal-9结合分子的候选物，并明确了哪个分子是Ga-9诱导的细胞凋亡的Gal-9结合分子。

项目成果

Kageshita T. et al.: "Possible role of galectin-9 in cell aggregation and apoptosis of human melanoma cell lines and its clinical significance"Int.J.Cancer. 99. 809-816 (2002)

Kageshita T.等人：“半乳糖凝集素9在人黑色素瘤细胞系的细胞聚集和凋亡中的可能作用及其临床意义”Int.J.Cancer。

Asakura H. et al.: "Selective eosinophil adhesion to fibroblast via IFN-γ-induced galectin-9"J.Immunol.. 169. 5912-5918 (2002)

Asakura H.等人：“通过IFN-γ诱导的半乳糖凝集素9选择性嗜酸性粒细胞粘附到成纤维细胞”J.Immunol.. 169. 5912-5918 (2002)

平島光臣: "新しい生理活性レクチン-ガレクチン9の基礎と臨床"日本皮膚科学会雑誌. 112(13). 1667-1669 (2002)

Mitsuomi Hirashima：“新型生物活性凝集素 - 半乳糖凝集素 9 的基础和临床方面”，日本皮肤病学会杂志 112(13) (2002)。

Kashio Y. et al.: "Galectin-9 induces apoptosis through calcium-calpain-caspase-1 pathway"J.Immunol.. (in press). (2003)

Kashio Y. 等人：“Galectin-9 通过钙-钙蛋白酶-caspase-1 途径诱导细胞凋亡”J.Immunol..（出版中）。

Imaizumi T. et al.: "15-deoxy-delta 12, 14-prostaglandin J2 inhibits IFN-gamma-induced galectin-9 expression in cultured human umbilical vein endothelial cells"Int. Arch, Allergy Immunol.. in press. (2003)

Imaizumi T. 等人：“15-脱氧-δ 12, 14-前列腺素 J2 抑制培养的人脐静脉内皮细胞中 IFN-γ 诱导的半乳糖凝集素 9 表达”Int。