Study on the molecular mechanism of antiangiogenesis by caspin/PEDF/EPC-1

Caspin/PEDF/EPC-1抗血管生成的分子机制研究

• 批准号: 14570205
• 负责人: SAGA Shinsuke
• 金额: $ 2.43万
• 依托单位: Aichi Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570205/
• 关键词: caspin; PEDF; angiogenesis; apoptosis; cartilage; bone; ECM; 内軟骨骨化; 膜性骨化; EPC-1

In the endochondral ossification, chondrocytes in the growth plate change the phenotypes and form proliferative, mature and hypertrophic cartilage. Subsequently, hypertrophic cartilage is replaced by bone tissue through vascular invasion and resorption. However, the regulatory mechanism of vascular invasion in endochondral ossification is unknown. Cartilage is generally avascular and resistant to vascular invasion. However, hypertrophic cartilage is invaded by blood vessels during endochondral ossification. Vascular invasion (angiogenesis) is thought to be regulated by the balance of angiogenesis inducers and inhibitors. In this study we investigated the role of caspin/PEDF/EPC-1, which is a novel intrinsic anti-angiogenic factor, in the differentiation and the embryonic morphogenesis of cartilage tissue. The expression and distribution of caspin molecules in 15.5 day mouse embryos was analyzed by the immunohistochemical method and in situ hybridization. Both the immature mesenchymal cells and the mature cartilage cells expressed caspin mRNA or protein, and the expression was reduced and disappeared during transformation to the hypertrophic cartilage. Prominent deposition of caspin was detected in the region surrounding hypertrophic cartilage cells. It seems to behave as the inhibitor of vascular invasion into cartilage tissue. ATDC5 cells, mouse clonal chondrogenic cell line, which reflect the multistep process of chondrogenic differentiation from mesenchymal condensation to calcification in vitro. In this study, the expression of caspin and other factors during in vitro endochondral ossification with ATDC5 cells, was analyzed especially focusing on angiogenic and anti-angiogenic factors. Caspin was expressed in ATDC5 cells before the expression of type X collagen which is characterized in hypertrophic cartilage cells. Caspin was reduced and diminished in the differentiated ATDC5 cells.

在软骨内成骨中，生长板中的软骨细胞改变表型，形成增殖性、成熟性和肥大性软骨。随后，肥大的软骨通过血管侵入和吸收被骨组织取代。然而，软骨内骨化中血管侵入的调控机制尚不清楚。软骨通常是无血管的，对血管的侵袭具有抵抗力。然而，肥大的软骨在软骨内骨化过程中会受到血管的侵袭。血管侵袭(血管生成)被认为是由血管生成诱导物和抑制物的平衡调节的。本研究探讨了Caspin/PEDF/EPC-1这一新的内源性抗血管生成因子在软骨组织分化和胚胎形态发生中的作用。应用免疫组织化学和原位杂交技术分析Caspin分子在15.5天小鼠胚胎中的表达和分布。未成熟间充质细胞和成熟软骨细胞均表达Caspin mRNA或蛋白，在向肥大软骨转化的过程中表达减弱或消失。在肥大的软骨细胞周围可见明显的Caspin沉积。它似乎是血管侵入软骨组织的抑制因子。ATDC5细胞，小鼠克隆性成软骨细胞系，在体外反映了从间充质凝聚到钙化的多步骤软骨分化过程。本研究分析了Caspin等因子在ATDC5细胞软骨内成骨过程中的表达，重点分析了血管生成因子和抗血管生成因子在软骨内成骨中的作用。Caspin在ATDC5细胞中的表达先于X型胶原的表达，而X型胶原的表达是肥大软骨细胞的特征。在分化的ATDC5细胞中，Caspin表达减少且减少。

项目成果

Increased expression of COX-2 in the development of human lung cancers.

• DOI: 10.1615/jenvironpatholtoxicoloncol.v21.i2.110
• 发表时间: 2002
• 期刊: Journal of environmental pathology, toxicology and oncology : official organ of the International Society for Environmental Toxicology and Cancer
• 作者: Takashi Takahashi;K. Kozaki;Y. Yatabe;H. Achiwa;T. Hida

He, Y., et al.: "Suppression of tumor lymphangiogenesis and lymph node metastasis by blocking vascular endothelial growth factor receptor 3 signaling"J. Natl. Cancer Inst.. 94. 819-825 (2002)

He, Y., et al.：“通过阻断血管内皮生长因子受体 3 信号传导抑制肿瘤淋巴管生成和淋巴结转移”J.

Takasu S, et al.: "Radioimmunoscintigraphy of intracranial glioma xenograft with a technetium-99m-labeled mouse monoclonal antibody specifically recognizing type III mutant epidermal growth factor receptor"J. Neuro-Oncol. 63. 247-256 (2003)

Takasu S 等人：“使用锝-99m 标记的小鼠单克隆抗体特异性识别 III 型突变表皮生长因子受体对颅内神经胶质瘤异种移植物进行放射免疫闪烁扫描”J.

Significant growth inhibition of human lung cancer cells both in vitro and in vivo by the combined use of a selective cyclooxygenase 2 inhibitor, JTE-522, and conventional anticancer agents.

• 发表时间: 2002-07
• 期刊: Clinical cancer research : an official journal of the American Association for Cancer Research
• 作者: T. Hida;K. Kozaki;Hidemi Ito;O. Miyaishi;Y. Tatematsu;Takeshi Suzuki;K. Matsuo;T. Sugiura;M. Ogawa;Toshitada Takahashi;Takashi Takahashi

Further investigation of the epitope recognized by the new monoclonal antibody 2C9.

进一步研究新型单克隆抗体2C9识别的表位。

• 发表时间: 2003
• 期刊: Int J Urol. 10
• 作者: Kato;K. et al.
• 通讯作者: K. et al.