Université de Nantes, France.
Drug Discov Today. 2010 Jul;15(13-14):553-60. doi: 10.1016/j.drudis.2010.05.009. Epub 2010 May 27.
Proteoglycans, extracellular matrix components, exert several activities on bone cells and seem crucial for maintaining an appropriate number of osteoblasts and osteoclasts. The overall data strengthen a pro-bone resorptive role for proteoglycans, through the control of osteoprotegerin availability and of receptor activator of NF-kappaB ligand bioactivity. In parallel, proteoglycans participate in the control of tumor development at different levels, including bone tumor development and bone metastases dissemination. This dual role makes them good candidates as regulatory molecules in the vicious cycle between tumor proliferation and bone resorption observed during tumor development in bone site. Knowledge of the biological roles of these molecules in cancer biology, tumor angiogenesis and metastasis has promoted the development of drugs targeting them.
蛋白聚糖是细胞外基质的组成成分,对骨细胞具有多种活性,似乎对维持适当数量的成骨细胞和破骨细胞至关重要。这些数据总体上表明,蛋白聚糖通过控制骨保护素的可用性和 NF-κB 配体生物活性,发挥促骨吸收作用。同时,蛋白聚糖参与肿瘤发展的多个水平的调控,包括骨肿瘤的发生和骨转移的扩散。这种双重作用使它们成为肿瘤在骨部位生长过程中观察到的肿瘤增殖与骨吸收之间恶性循环的调节分子的良好候选物。这些分子在癌症生物学、肿瘤血管生成和转移中的生物学作用的知识促进了针对这些分子的药物的开发。