Weber G F, Ashkar S, Cantor H
Dana-Farber Cancer Institute, Division of Immunopathology, Boston, MA 02115, USA.
Proc Assoc Am Physicians. 1997 Jan;109(1):1-9.
Malignant growth has been associated with oncogene activation, telomerase activity, and expression of CD44 splice variants on the cell surface. Though dysregulation of growth control due to expression of oncogene products is fairly well understood, the mechanism of CD44-mediated homing and colony formation in specific tissues has remained cryptic. We have identified the cytokine osteopontin as a ligand for CD44. Osteopontin binds to naturally expressed and stably transfected CD44 in a manner that is specific, dose-dependent, inhibitable by anti-CD44 antibodies, insensitive to competition by Gly-Arg-Gly-Asp-Ser, and sensitive to competition by hyaluronate. The receptor-ligand interaction mediates chemotaxis or attachment, depending on presentation of osteopontin in soluble or immobilized form. In contrast, binding of CD44 to hyaluronate mediates aggregation or attachment but not chemotaxis. We found that two events occurring in malignancy-secretion of osteopontin and expression of CD44v-are linked in such a way that they may cause migration of tumor cells to specific sites of metastasis formation.
恶性生长与癌基因激活、端粒酶活性以及细胞表面CD44剪接变体的表达有关。尽管由于癌基因产物的表达导致生长控制失调已得到较好的理解，但CD44介导的在特定组织中归巢和集落形成的机制仍不清楚。我们已确定细胞因子骨桥蛋白是CD44的一种配体。骨桥蛋白以一种特异性、剂量依赖性的方式与天然表达和稳定转染的CD44结合，可被抗CD44抗体抑制，对甘氨酸-精氨酸-甘氨酸-天冬氨酸-丝氨酸的竞争不敏感，而对透明质酸的竞争敏感。受体-配体相互作用介导趋化作用或附着，这取决于骨桥蛋白以可溶性或固定化形式的呈现。相反，CD44与透明质酸的结合介导聚集或附着，但不介导趋化作用。我们发现，在恶性肿瘤中发生的两个事件——骨桥蛋白的分泌和CD44v的表达——以这样一种方式联系在一起，即它们可能导致肿瘤细胞迁移至转移形成的特定部位。
