Structure and function of a new member of ectophosphodiesterase I

外切磷酸二酯酶I新成员的结构与功能

• 批准号: 12670135
• 负责人: SANO Kimihiko
• 金额: $ 2.37万
• 依托单位: Kobe University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12670135/
• 关键词: CD203c; cancer metastasis; cancer infiltration; E-NPP1; E-NPP3; bile duct carcinoma ; cholangiocarcinoma ; carcinogenesis; ホスホジエステラーゼ; アレルギー; 好塩基球; マスト細胞; がんの浸潤、転移; モノクローナル抗体

E-NPP (ecto-nucleotide pyrophosphatase/phosphodiesterase I) consists of three closely related molecules. E-NPP1 (PC-1) was first cloned as a plasma cell differentiating antigen. E-NPP-2 (autotaxin) was purified as an autocrine tumor cell motility stimulation factor from melanoma cells. And E-NPP3 was cloned from human prostate CDNA library. Forced overexpression of E-NPP3 gives fibroblasts and glioma cells an invasive property. We have investigated the expression and localization of E-NPP1 and 3 in human neoplastic bile duct diseases. Western blot analysis revealed that expression of E-NPP3 but not E-NPP1 was higher in tumor tissues than in surrounding tissues. Immunohistochemical analysis demonstrated that E-NPP1 was located at apical side of tumor cells while E-NPP3 was at the apical plasma membrane. Cleaved form of E-NPP3 protein but not E-NPP1 was readily detected in the cholangiocarcinoma patients' sera. In situ hybridization confirmed the presence of E-NPP1 and -3 mRNA in tumor tissues. Furthermore, NIH3T3 cells that stably transfected with E-NPP3 CDNA (NIH3T3/E-NPP3 cells) but not NIH3T3/E-NPP1 cells showed increased migration rate through collagen-coated membranes. These results suggest that E-NPP3 is involved in tumor cell infiltration of bile duct carcinoma and cholangiocarcinoma.

E-NPP（外核苷酸焦磷酸酶/磷酸二酯酶I）由三种密切相关的分子组成。E-NPP 1（PC-1）首先作为浆细胞分化抗原被克隆。E-NPP-2（autotaxin）是从黑素瘤细胞中纯化的自分泌肿瘤细胞运动刺激因子。从人前列腺cDNA文库中克隆了E-NPP 3。E-NPP 3的强制过表达赋予成纤维细胞和神经胶质瘤细胞侵袭性。我们研究了E-NPP 1和3在人胆管肿瘤性疾病中的表达和定位。Western blot分析显示，E-NPP 3在肿瘤组织中的表达高于癌旁组织，而E-NPP 1则无表达。免疫组化结果显示E-NPP 1定位于肿瘤细胞的顶侧，E-NPP 3定位于肿瘤细胞的顶侧质膜。胆管癌患者血清中易检测到E-NPP 3蛋白的裂解形式，而E-NPP 1蛋白则不存在。原位杂交证实肿瘤组织中存在E-NPP 1和-3 mRNA。此外，用E-NPP 3 cDNA稳定转染的NIH 3 T3细胞（NIH 3 T3/E-NPP 3细胞）而不是NIH 3 T3/E-NPP 1细胞显示出通过胶原包被的膜的迁移率增加。这些结果表明，E-NPP 3参与了胆管癌和胆管癌的肿瘤细胞浸润。

项目成果

Sugahara K.: "Mice lacking CCAAT/enhancer-binding protein"Cell Tissue Res. 306. 57-63 (2001)

Sugahara K.：“缺乏 CCAAT/增强子结合蛋白的小鼠”细胞组织研究。

Rutsch, F., Vaingankar, S., Johnson, K.A., Goldfine, I., Maddux, B., Schauerte, P., Kalhoff, H., Sano, K., Boisvert, W.A., Superti-Furga, A., and Terkeitaub, R.: "PC-1 Nucleoside triphosphate pyrophosphohydrolase deficiency in idiopathic infantile arteria

Rutsch, F.、Vaingankar, S.、Johnson, K.A.、Goldfine, I.、Maddux, B.、Schauerte, P.、Kalhoff, H.、Sano, K.、Boisvert, W.A.、Superti-Furga, A.,

Sano, K: "Structure of AF^3p^<21>"Leukemia Lymphoma. 42・4. 595-602 (2001)

Sano，K：“AF^3p^<21>的结构”白血病淋巴瘤42・4（2001）。

KUmaki, S., Ishii, N., Minegishi, M., Ohashi, Y., Hakozaki, I., Nonoyama, S., Imai, K., Morio, T., Tsuge, I. Sakiyama, Y., Miyanoshita, A., Miura, J., Mayumi, M., Heike, T., Katamura, K., Takada, H., Izumi, I., Kamizono, J., Hibi, S., Sasaki, H., Kimura,

熊木 S.、石井 N.、峰岸 M.、大桥 Y.、箱崎 I.、野野山 S.、今井 K.、森尾 T.、柘植 I.、崎山 Y.、宫之下

Biihring HJ.: "The basophil activation marker defined by antibody 97A6 is identical with the E-NPY3"Blood. 97・10. 3303-3305 (2001)

Biihring HJ.：“抗体 97A6 定义的嗜碱性粒细胞激活标记与 E-NPY3 相同”Blood.