CARBOHYDRATE DEPENDENT ADHESION OF NORMAL & TUMOR CELLS

本项目研究的结构，生物合成，和作用， 细胞间通讯中的选择素配体。 它还旨在阐明 选择素与糖类相互作用在肿瘤细胞中的作用 转移 该项目是一个密切合作， 研究人员的专长包括碳水化合物合成 化学，碳水化合物化学，碳水化合物生物合成，细胞 和分子生物学。 工作围绕唾液酸Lex和相关寡糖展开 结构最初发现的参与者在这个赠款作为E- 选择素配体。 E-、P-和L-选择素的结构和生物合成 将研究人和小鼠中的配体。 特别是，角色 选择素配体形成中的特异性岩藻糖基转移酶 而呈递选择素配体的N-聚糖的那些将通过以下测定： 使用基因敲除小鼠。 此外，还研究了其结构和生物合成。 寡糖L-选择素配体将通过克隆 形成配体的酶。 选择素配体生物合成的调节将在 涉及的酶的亚细胞定位的关系， 选择素配体的生物合成。 该项目还旨在 确定选择素介导的粘附在肿瘤细胞中的作用 传播。 这些研究将为选择素-碳水化合物的研究提供新的信息 相互作用，并可能有助于设计改进的治疗方法， 对恶性肿瘤和其他疾病的干预。

This program project examines the structure, biosynthesis, and roles of selectin ligands in cell-cell communication. It also aims at elucidating the roles of the selectin-carbohydrate interaction in tumor cell metastasis. This program project is a close collaboration among investigators whose expertise range from carbohydrate synthetic chemistry, carbohydrate chemistry, carbohydrate biosynthesis, to cellular and molecular biology. The work centers around the sialyl Lex and related oligosaccharide structures originally discovered by the participants in this grant as E- selectin ligands. Structure and biosynthesis of E-, P- and L-selectin ligands in human and mice will be investigated. In particular, the roles of specific fucosyltransferase(s) in the formation of selectin ligands and those of N-glycans presenting selectin ligands will be determined by using knock-out mice. In addition, the structure and biosynthesis of the oligosaccharide L-selectin ligand(s) will be elucidated by cloning an enzyme that forms the ligand(s). The regulation of selectin ligand biosynthesis will be investigated in relation to subcellular localization of the enzymes involved in the biosynthesis of selectin ligands. This program project also aims at determining the roles of selectin-mediated adhesion in tumor cell dissemination. These studies will provide new information on selectin-carbohydrate interactions and may help in the design of improved therapeutic intervention in malignancies and other diseases.