Carbohydrate-Dependent Adhesion in Normal and Tumor Cells

描述(由申请者提供)：该项目研究碳水化合物的结构、生物合成和在细胞-细胞相互作用中的作用。拟议的项目是我们在上一个资助期开展的强有力的合作研究活动的证明。该计划项目是研究人员之间持续密切的合作，他们的专业知识范围从碳水化合物合成化学、碳水化合物生物合成、免疫学到细胞和分子生物学。在接下来的几年里，我们将通过结合活体显微镜来观察体内细胞的迁移和相互作用，从而增强研究能力。这项工作主要集中在硫化、岩藻糖化的糖偶联物在淋巴细胞运输、肿瘤进展和骨髓生成中的作用。这项工作包括通过研究岩藻糖在Notch信号转导中的作用，研究糖介导的信号转导的作用，这是该领域的一个新方面。这项工作还通过识别新的碳水化合物识别分子及其对肿瘤靶向的使用，以及确定硫酸乙酰肝素在肿瘤血管生成中的作用，确定了碳水化合物依赖的肿瘤转移的作用。这些研究将提供有关碳水化合物在骨髓生成、慢性炎症、肿瘤进展和碳水化合物依赖的信号转导中的作用的新信息。从这些研究中获得的知识可能有助于设计改进的针对恶性肿瘤和其他疾病的治疗干预措施。

DESCRIPTION (provided by applicant): This program project examines the structure, biosynthesis, and roles of carbohydrates in cell-cell interaction. The proposed projects were borne-out from our strong collaborative research activities in the previous funding period. This program project is a continued close collaboration among investigators whose expertise ranges from carbohydrate synthetic chemistry, carbohydrate biosynthesis, immunology, to cellular and molecular biology. In the coming years, we will add strength in research capability by incorporating intravital microscopy to observe migrating and interacting cells in vivo. The work centers around sulfated, fucosylated glycoconjugates in lymphocyte trafficking, tumor progression, and myelopoiesis. The work includes the role of carbohydrate-mediated signal transduction, a novel aspect in the field, through studies on the role of fucose in Notch signaling. The work also determines the role of carbohydrate-dependent tumor metastasis by identifying novel carbohydrate recognition molecules and their use for tumor targeting, and determining the roles of heparan sulfate in tumor angiogenesis. These studies will provide new information on the roles of carbohydrates in myelopoiesis, chronic inflammation, tumor progression, and carbohydrate-dependent signal transduction. The knowledge gained from these studies may help in the design of improved therapeutic intervention against malignancies and other diseases.