Carbohydrate-Dependent Adhesion in Normal and Tumor Cells

描述（由申请人提供）：本项目研究碳水化合物在细胞-细胞相互作用中的结构、生物合成和作用。建议的项目是由我们在上一个资助期进行的强有力的合作研究活动所完成的。该项目是碳水化合物合成化学、碳水化合物生物合成、免疫学、细胞和分子生物学等领域研究人员之间持续密切合作的结果。在未来几年，我们将加强研究能力，结合活体显微镜观察细胞在体内的迁移和相互作用。这项工作主要围绕在淋巴细胞运输、肿瘤进展和骨髓形成中的硫酸化、聚焦化糖缀合物展开。这项工作包括碳水化合物介导的信号转导的作用，这是该领域的一个新方面，通过研究聚焦在Notch信号传导中的作用。这项工作还通过鉴定新的碳水化合物识别分子及其在肿瘤靶向中的应用，确定了碳水化合物依赖性肿瘤转移的作用，并确定了硫酸肝素在肿瘤血管生成中的作用。这些研究将为碳水化合物在骨髓形成、慢性炎症、肿瘤进展和碳水化合物依赖性信号转导中的作用提供新的信息。从这些研究中获得的知识可能有助于设计针对恶性肿瘤和其他疾病的改进的治疗干预措施。

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.