Identification and funs tonal analysis of novel molecules that regulate tumor cell motility

我们发现肿瘤转移相关的细胞表面分子CD44不仅可以识别透明质酸（GlcA- glcnac），还可以识别硫酸软骨素（GlcA /Ido-A-GaINAc）的必需部分。这表明CD44可以与血管内皮细胞以及细胞外基质（ECM）成分表达的各种蛋白聚糖相互作用。此外，我们发现透明质酸（HA）降解成一定大小范围的寡糖，可以诱导肿瘤细胞的CD44蛋白水解裂解，促进肿瘤细胞的运动。此外，我们发现肿瘤细胞本身产生透明质酸酶，可以产生HA寡糖，HA寡糖反过来与肿瘤细胞CD44结合，促进CD44裂解和肿瘤运动。其他类型的糖胺聚糖在降解为低聚物时也表现出类似的活性。这些结果提示肿瘤细胞及其ecm可产生促进肿瘤细胞侵袭的物质。我们还对趋化因子和趋化因子结合分子进行了研究，发现趋化因子固定在某些ECM成分上时，可以有效地诱导细胞定向运动。

We have found that a tumor metastasis-related cell surface molecule CD44 can recognize not only hyaluronic acid (GlcA-GlcNAc) but also an essential moiety of chondroitin sulfate, GlcA/Ido-A-GaINAc. This indicates that CD44 can interact with various proteoglycans expressed by vascular endothelial cells as well as extracellular matrix (ECM) components. In addition, we found that hyaluronan (HA) degraded into oligosaccharides of a certain size range can induce proteolytic cleavage of CD44 from tumor cells and promote tumor cell motility. Furthermore, we found that tumor cells themselves produce hyaluronidases that can generate HA oligosaccharides, which in turn bind to tumor cell CD44 to promote CD44 cleavage and tumor motility. Other types of glycosaminoglycans also showed similar activities when they were degraded into oligomers. These results suggest that tumor cells and their ECMs can generate substances that promote tumor cell invasion. We have also made investigations on chemokines and chemokine binding molecules and found that chemokines can induce directional cell motility efficiently when they are immobilized on certain ECM components.