Glyco-Signals in Regulatory Mechanisms For Proliferation, Differentiation, Senescence And Apoptosis of Hematopoietic Cells.

造血细胞增殖、分化、衰老和凋亡调节机制中的糖信号。

基本信息

批准号：
08457270
负责人：
SAITO Masaki
金额：
$ 4.99万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1996
资助国家：
日本
起止时间：
1996 至 1997
项目状态：
已结题

项目摘要

During the period from 1996 to 1997, the following new findings were obtained, and most of them were presented in some of the international conferences, and published in the specialized journals : (1) The interaction of the extracellular matrix glycoprotein, fibronectin, with the integrin VLA-5 was shown to be intimately related with the apoptotic phenomena of hematopoietic cells. (2) A significant enhancement of the expression of VLA-5 mRNA was observed only in the monocytic, but not granulocytic, differentiation of human myelogenous leukemia HL-60 cells. (3) The expression of integrin VLA-5 on the cell surface was enhanced exclusively in the process of monocytic differentiation, and the most prominent expression was observed on the surface of peripheral mature monocytes. (4) The sensitivity of fibronectin-induced apoptosis was remarkably increased during monocytic differentiation, and the anti-VLA-5 monoclonal antibody or the RGD peptide completely abolished it. (5) Apoptosis of the … More normal monocytes, but not granulocytes, from peripheral blood was significantly increased by the extracellular matrix fibronectin, and the anti-fibronectin monoclonal antibody suppressed the apoptosis and increased the survival time of normal monocytes. (6) Expression of the extracellular matrix glycoprotein, tenascin, was restricted spatially and temporally during the formation of tumor tissues, depending upon the stromal-epithelial interactions, and the de novo synthesis of tenascins was induced by the soluble growth factor EGF,being also dependent on the stromal-epithelial interactions. Human tenascin C is shown to have the EGF-like domain, but this domain and its derivative peptide could not induce the expression of tenascin. (7) With all the current data taken together, it is concluded that the ECM glycoprotein fibronectin might play an important role as the negative regulator for the survival of monocytes in collaboration with the integrin VLA-5, which characteristically increases during the process of monocytic differentiation.In the latter part of the present research projects, the following novel findings were demonstrated : (8) Using the elaborately-devised expression cloning method, we have succeeded for the first time in isolating and molecularly characterizing a new and relevant gene (cDNA and its genome) which encodes a key glycosyltransferase, ganglioside GM3 synthase (sialyltransferase-1) , responsible for the biosynthesis of a ubiquitous but intriguing membraneous molecule of the simplest structure, ganglioside GM3. GM3 was previously demonstrated to exhibit a variety of biological functions intimately related to the cell growth control, malignant transformations, the cell-to-cell recognitions, and the differentiation-induction of human myelogenousleukemia cells. Less