ROLE OF GLYCOCONJUGATES IN TUMOR CELL ADHESION

糖复合物在肿瘤细胞粘附中的作用

• 批准号: 5200997
• 负责人: D D ROBERTS
• 金额: --
• 依托单位: DIVISION OF CANCER BIOLOGY AND DIAGNOSIS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/5200997
• 关键词: angiogenesis; apolipoproteins; cell adhesion; cell adhesion molecules; extracellular matrix; gene expression; glycolipids; glycoproteins; heparan sulfate; heparin; human tissue; laminin; neoplastic cell; neoplastic growth; proteoglycan; selectins; small cell lung cancer; sulfates; thrombospondins; tissue /cell culture; vascular endothelium

Altereed glycosylation of glycolipids, glycoproteins, or proteoglycans are frequently observed in tumor tissues and cultured cancer cell lines. These changes have diagnostic use but also can contribute to the ability of tumor cells to grow, induce neovascularization, metastasize, and avoid host immune surveillance. We are primarily interested in sulfated glycoconjugates and their interaction with extracellular matrix and cell surface adhesion molecules. These include thrombospondin, laminin, selectins, and apolipoprotein E. Human small cell lung carcinoma cell lines are used to examine expression and function of novel sulfated glycolipids. These glycolipids interact with thrombospondin and contribute to adhesion of SCLC cells on a thrombospondin matrix. Sulfated glycolipids on these cells are also being examined as potential ligands for selectin- mediated adhesion of SCLC cells to activated endothelium. Heparin oligosaccharides are being used to define the molecular basis for interactions of heparin and heparan sulfate proteoglycans with two binding motifs on the thrombospondin molecule and on a second heparin- binding protein, apolipoprotein E. Inhibitors of these interactions are being tested for effects on angiogenesis and tumor growth.

糖脂、糖蛋白或蛋白聚糖的糖基化改变 在肿瘤组织和培养的癌细胞中经常观察到 线 这些变化具有诊断用途，但也有助于 肿瘤细胞生长，诱导新血管形成， 转移，避免宿主免疫监视。 我们主要 对硫酸化糖缀合物及其与 细胞外基质和细胞表面粘附分子。 这些 包括血小板反应蛋白、层粘连蛋白、选择素和载脂蛋白E。 人小细胞肺癌细胞系用于检查 新型硫酸化糖脂的表达和功能。 这些 糖脂与血小板反应蛋白相互作用， 血小板反应蛋白基质上的SCLC细胞。 硫酸化糖脂 细胞也被作为选择素的潜在配体进行研究， 介导SCLC细胞与活化内皮的粘附。 肝素 低聚糖被用来定义的分子基础， 肝素和硫酸乙酰肝素蛋白聚糖与两种 - 所述血小板反应蛋白分子上和第二肝素上的结合基序， 结合蛋白，载脂蛋白E。 这些相互作用的抑制剂 正在测试对血管生成和肿瘤生长的影响。