Rubin Janet, Fan Xian, Rahnert Jill, Sen Buer, Hsieh Chia-Ling, Murphy Tamara C, Nanes Mark S, Horton Lindsay G, Beamer Wesley G, Rosen Clifford J
Department of Medicine, Emory University & VAMC, Decatur, Georgia.
Prostate. 2006 Jun 1;66(8):789-800. doi: 10.1002/pros.20379.
BACKGROUND: IGF-I is an important growth and differentiative factor for osteoblasts and may have a role in defining prostate cancer risk and skeletal metastases. METHODS: Conditioned media (CM) from human prostate cancer (PC), C4-2 and C4-2B, which produce osteoblastic lesions, and PC-3, which causes osteolysis, was added to MC3T3-E1 bone cultures. SCID mice were injected intratibially with these engineered cells. Tumor bearing tibiae were analyzed by microCT and pQCT. RESULTS: CM from PC cells increased osteoblast proliferation and differentiation and was unaltered by the type of PC cell, IGF-I antibodies, or exogenous IGF-I and IGFBP2. Study of intratibial PC tumors in SCID mice showed that C4-2 cells grew slowly preserving bone structure, while PC-3 tumors caused rapid osteolysis. Overexpression of IGF-I did not change either tumor progression or skeletal response. CONCLUSIONS: IGF-I is neither necessary nor sufficient for the osteoblastic response to PC metastases.
背景：胰岛素样生长因子-I（IGF-I）是成骨细胞重要的生长和分化因子，可能在前列腺癌风险及骨转移的判定中发挥作用。 方法：将来自产生成骨病变的人前列腺癌（PC）细胞系C4-2和C4-2B以及导致骨质溶解的PC-3细胞系的条件培养基（CM）添加到MC3T3-E1骨培养物中。将这些经过工程改造的细胞经胫骨内注射到重症联合免疫缺陷（SCID）小鼠体内。通过显微计算机断层扫描（microCT）和外周定量计算机断层扫描（pQCT）对荷瘤胫骨进行分析。 结果：PC细胞系的CM可增加成骨细胞的增殖和分化，且不受PC细胞类型、IGF-I抗体或外源性IGF-I和胰岛素样生长因子结合蛋白2（IGFBP2）的影响。对SCID小鼠胫骨内PC肿瘤的研究表明，C4-2细胞生长缓慢，可保留骨结构，而PC-3肿瘤则导致快速骨质溶解。IGF-I的过表达既未改变肿瘤进展，也未改变骨骼反应。 结论：IGF-I对于PC转移的成骨反应既非必需，也不充分。
Int J Cancer. 2011-3-28
Zotero 插件