Identification and funs tonal analysis of novel molecules that regulate tumor cell motility

调节肿瘤细胞运动的新型分子的鉴定和趣味分析

• 批准号: 12219211
• 负责人: MIYASAKA Masayuki
• 金额: $ 100.54万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research on Priority Areas
• 财政年份: 2000
• 资助国家: 日本
• 起止时间: 2000 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-12219211/
• 关键词: CD44; hyaluronic acid; hyaluronidase; P-selectin; PSG L-1; extracellular matrix; metastasis; グリコサミノグリカン; 細胞接着; 血管内皮細胞; 癌転移; セレクチン; リポソーム; 癌細胞ローリング; 血行性転移; プロテオグリカン

We have found that a tumor metastasis-related cell surface molecule CD44 can recognize not only hyaluronic acid (GlcA-GlcNAc) but also an essential moiety of chondroitin sulfate, GlcA/Ido-A-GaINAc. This indicates that CD44 can interact with various proteoglycans expressed by vascular endothelial cells as well as extracellular matrix (ECM) components. In addition, we found that hyaluronan (HA) degraded into oligosaccharides of a certain size range can induce proteolytic cleavage of CD44 from tumor cells and promote tumor cell motility. Furthermore, we found that tumor cells themselves produce hyaluronidases that can generate HA oligosaccharides, which in turn bind to tumor cell CD44 to promote CD44 cleavage and tumor motility. Other types of glycosaminoglycans also showed similar activities when they were degraded into oligomers. These results suggest that tumor cells and their ECMs can generate substances that promote tumor cell invasion. We have also made investigations on chemokines and chemokine binding molecules and found that chemokines can induce directional cell motility efficiently when they are immobilized on certain ECM components.

我们已经发现肿瘤转移相关的细胞表面分子CD 44不仅可以识别透明质酸（GlcA-GlcNAc），而且可以识别硫酸软骨素的必需部分GlcA/Ido-A-GaINAc。这表明CD 44可以与血管内皮细胞表达的各种蛋白聚糖以及细胞外基质（ECM）组分相互作用。此外，我们发现透明质酸（HA）降解为一定大小范围的寡糖可以诱导肿瘤细胞上的CD 44蛋白水解切割，并促进肿瘤细胞的运动。此外，我们发现肿瘤细胞本身产生透明质酸酶，该酶可以产生HA寡糖，HA寡糖进而与肿瘤细胞CD 44结合以促进CD 44切割和肿瘤运动。其他类型的糖胺聚糖在降解成低聚物时也表现出类似的活性。这些结果表明，肿瘤细胞及其ECM可以产生促进肿瘤细胞侵袭的物质。我们还对趋化因子和趋化因子结合分子进行了研究，发现当趋化因子固定在某些ECM组分上时，它们可以有效地诱导定向细胞运动。

项目成果

Characterization of mac25/angiomodulin expression by high endothelial venule cells in lymphoid tissues and its identification as an inducible marker for activated endothelial cells

• DOI: 10.1093/intimm/dxf102
• 发表时间: 2002-11-01
• 期刊: INTERNATIONAL IMMUNOLOGY
• 影响因子: 4.4
• 作者: Usui, T;Murai, T;Miyasaka, M
• 通讯作者: Miyasaka, M

Kawashima, H.et al.: "Collagen XVIII, a basement membrane heparan sulfate proteoglycan, interacts with L-selectin and monocyte chemoattractant protein-1"Journal of Biological Chemistry. (In press).

Kawashima, H.等人：“XVIII 胶原蛋白，一种基底膜硫酸乙酰肝素蛋白聚糖，与 L-选择素和单核细胞趋化蛋白-1 相互作用”《生物化学杂志》。

Sulfatide binding and activation of leukocytes through an L-selectin-independent pathway.

硫脂苷通过不依赖于 L-选择素的途径结合并激活白细胞。

• 发表时间: 2000
• 期刊: J.Leuk.Biol. 68
• 作者: Ding;Z. et al.
• 通讯作者: Z. et al.

Hyaluronan Recognition Mode of CD44 Revealed by Cross-saturation and Chemical Shift Perturbation Experiments

交叉饱和和化学位移扰动实验揭示了 CD44 的透明质酸识别模式

• 发表时间: 2003
• 期刊: J. Biol. Chem. 278
• 作者: Takeda M;Terasawa H;Sakakura M;Yamaguchi Y;Kiajiwara M;Kawashuima H;Miyasaka M;Shimada I
• 通讯作者: Shimada I

Gene expression profiling of mucosal addressin cell adhesion molecule-1+ high endothelial venule cells (HEV) and identification of a leucine-rich HEV glycoprotein as a HEV marker

• DOI: 10.4049/jimmunol.168.3.1050
• 发表时间: 2002-02-01
• 期刊: JOURNAL OF IMMUNOLOGY
• 影响因子: 4.4
• 作者: Saito, K;Tanaka, T;Miyasaka, M
• 通讯作者: Miyasaka, M