STUDIES ON MOLECULAR MECHANISMS AND PHYSIOLOGICAL FUNCTIONS OF ANTI-CELL ADHESION

抗细胞粘附分子机制及生理功能研究

• 批准号: 07308073
• 负责人: KIMATA Koji
• 金额: $ 6.66万
• 依托单位: INSTITUTE FOR MOLECULAR SCIENCE OF MEDICINE,AICHI MEDICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07308073/
• 关键词: Cell adhesion; Anti-adhesion; Integrin; Extracellular matrix; Cell-substratum inteaction; Proteoglycans; Adhesion signal; kinases; 抗一接着; レセプター

Some of established cell lines are insensitive to anti-adhesive activity of chondroitin sulfate proteoglycans, and other lines are defective of annexin VI which is a candidate of the receptor for chondroitin sulfate chains with anti-adhesive activity. Those may be useful to analyze a possible role of annexin VI in anti-adhesion (Kimata). Transfection with antisense RNA for HSP-47 expression caused not only the decrease in collagen synthesis but also insolubilization of the collagen, which suggests a role of HSP-47 as shaperon (Nagata). Kitagawa analyzed the effect of the transfection with mutant laminin genes on the cell behaviors. Mammary carcinoma cells with high activity of tenascin production, compared to those with the low activity, showed the round cell morphology, the high activity of cell migration and the high invasiveness, which sugggests the effect of anti-adhesive activity of tenascin on the metastasis (Sakakura). In addition, differently from the anti-adhesion, RGD-indepen … More dent integrin may be involved in a cryptic cell-adhesive acitivity of tenascin (Obara). A novel membrane-bound proteoglycan, neuroglycan C influences cell adhesion in rat brain and may induce the neurite outgrowth (Oohira). lung carcinoma cells with the low metastatic activity usually show the high expression of syndecan and tend to show the organized stress fiber formation, but those with the high activity tend to induce the formation of ruffling membranes. The difference may explain a possible realationship between the cell adhesiveness and the metastatic ability of the carcinoma (Okayama). Sekiguchi has found that altemative splicing of fibronectin modulates the capacity for cell-adhesion. A brain proteoglycan with tyrosine phosphatase activity has been found to exhibit anti-adhesion activity to neuronal cells in the nervous center. This proteoglycan may function as a receptor for pleiotrophin (Noda). Sofue has suggested that laminin may be a IGF-I-dependent differentiation-inducing factor and further found the inbolvement of tyrosine phosphorylation in the signal transduction. Inagaki has succeeded in raising monoclonal antivodies to phosphorylated cytoskeletal proteins and revealed the possible relationship of the phosphorylation of intermediate filaments to the changes in cell-adhesion of proliferating cells. Tsukita has observed the activation of integrin when a cadherin-binding protein, b-catenin is forced to be expressed. The first and second group meetings were held in Nagoya to discuss results, give useful suggestions and comments each other and exchange current informations. Less

一些已建立的细胞系对硫酸软骨素蛋白聚糖的抗粘附活性不敏感，而另一些细胞系是膜联蛋白VI缺陷的，膜联蛋白VI是具有抗粘附活性的硫酸软骨素链的受体的候选者。这些可能有助于分析膜联蛋白VI在抗粘附中的可能作用（Kimata）。用HSP-47表达的反义RNA转染不仅引起胶原合成的减少，而且引起胶原的不溶解，这表明HSP-47作为shaperon（Nagata）的作用。Kitagawa分析了突变层粘连蛋白基因转染对细胞行为的影响。与低活性的乳腺癌细胞相比，高活性的乳腺癌细胞表现出圆形的细胞形态、高的细胞迁移活性和高的侵袭力，这证实了Tenascin的抗粘附活性在转移中的作用（Sakakura）。另外，与抗粘连不同， ...更多信息 齿状整合素可能参与腱生蛋白（Obara）的隐蔽细胞粘附活性。一种新型的膜结合蛋白聚糖，神经聚糖C影响大鼠脑中的细胞粘附，并可能诱导神经突生长（Oohira）。具有低转移活性的肺癌细胞通常表现出多配体蛋白聚糖的高表达，并且倾向于表现出有组织的应力纤维形成，但是具有高转移活性的肺癌细胞倾向于诱导褶皱膜的形成。这种差异可能解释了细胞增殖与癌转移能力之间的可能关系。Sekiguchi发现，纤连蛋白的可变剪接调节细胞粘附的能力。已发现具有酪氨酸磷酸酶活性的脑蛋白聚糖对神经中枢中的神经元细胞表现出抗粘附活性。这种蛋白聚糖可以作为多效生长因子（Noda）的受体起作用。Sofue认为层粘连蛋白可能是一种IGF-I依赖的分化诱导因子，并进一步发现酪氨酸磷酸化参与了信号转导。稻垣已成功地提高单克隆抗体磷酸化的细胞骨架蛋白，并揭示了可能的关系，磷酸化的中间丝的变化，在细胞粘附的增殖细胞。Tsukita已经观察到当钙粘蛋白结合蛋白，b-连环蛋白被迫表达时整合素的活化。第一次和第二次小组会议在名古屋举行，讨论结果，相互提出有用的建议和意见，并交流当前的信息。少

项目成果

Fukuoka, M. et al.: "Molecular cloning and expression of chick chondrocyte chondroitin 6-sulfotransferase" The Journal of Biological Chemistry. 270. 18575-18580 (1995)

Fukuoka, M. 等人：“鸡软骨细胞软骨素 6-磺基转移酶的分子克隆和表达”生物化学杂志。

Niimi,T.,K.and Kitagawa,Y.: "Expression of the long arm sequence of mouse laminin α1, β1 or γ1 chain COSI cells and assembly of monkey-mouse hybrid laminin." J. Biochem.(In press).

Niimi, T., K. 和 Kitakawa, Y.：“小鼠层粘连蛋白 α1、β1 或 γ1 链 COSI 细胞的长臂序列的表达以及猴-小鼠杂交层粘连蛋白的组装。”（正在出版）。

Kumagai,C.,Kadowaki,T.and Kitagawa,Y.: "Drosophila laminin assembly formining two types of αβγ trimers in Kc 167 cells" Matrix Biol.(In press).

Kumagai, C.、Kadowaki, T. 和 Kitakawa, Y.：“果蝇层粘连蛋白在 Kc 167 细胞中组装形成两种类型的 αβγ 三聚体”Matrix Biol。

Watanabe,E.,Kushima,Y.and Oohira,A.: "Heparan sulfate proteoglycan associated with growing parallel fibers of granule cells in the rat cerebellar cortex" Journal of Brain Science. 22. 67-75 (1996)

Watanabe，E.，Kushima，Y. 和 Oohira，A.：“硫酸乙酰肝素蛋白聚糖与大鼠小脑皮质中颗粒细胞平行纤维的生长有关”《脑科学杂志》。

Tokai,N.,Fujimoto-Nishiyama,A.,Toyoshima,Y.,Yonemura,S.,Tsukita,Sh.,Inoue,I.,and Yomamoto,T.: "Kid,a novel kinesin-like DNA binding protein,is localized to chromosomes and the mitotic spindle" EMBO Journal. 15. 457-467 (1996)

Tokai,N.、Fujimoto-Nishiyama,A.、Toyoshima,Y.、Yonemura,S.、Tsukita,Sh.、Inoue,I. 和 Yomamoto,T.：“Kid，一种新型驱动蛋白样 DNA 结合蛋白，