Kido J, Yamauchi N, Ohishi K, Kataoka M, Nishikawa S, Nakamura T, Kadono H, Ikedo D, Ueno A, Nonomura N, Okuyama A, Nagata T
Department of Periodontology and Endodontology, Tokushima University School of Dentistry, Japan.
J Cell Biochem. 1997 Nov 1;67(2):248-56.
Human prostatic carcinoma frequently metastasizes to bone tissue and activates bone metabolism, especially bone formation, at the site of metastasis. It has been reported that an extract of prostatic carcinoma and conditioned medium (CM) of a human prostatic carcinoma cell line, PC-3, established from a bone metastastic lesion, stimulate osteoblastic cell proliferation. However, there is little information about the effect of PC-3 CM on the differentiation of osteoblastic cells. In this study, we investigated the effect of PC-3 CM on the differentiation of two types of osteoblastic cells, primary fetal rat calvaria (RC) cells containing many undifferentiated osteoprogenitor cells, and ROS 17/2.8, a well-differentiated rat osteosarcoma cell line. PC-3 CM inhibited bone nodule formation and the activity of alkaline phosphatase (ALPase), an osteoblastic marker enzyme, on days 7, 14, and 21 (RC cells) or 3, 6, and 9 (ROS 17/2.8 cells) in a dose-dependent manner (5-30% CM). However, the CM did not affect cell proliferation or cell viability. PC-3 CM was found to markedly block the gene expression of ALPase and osteocalcin (OCN) mRNAs but had no effect on the mRNA expression of osteopontin (OPN), the latter two being noncollagenous proteins related to bone matrix mineralization. These findings suggest that PC-3 CM contains a factor that inhibits osteoblastic cell differentiation and that this factor may be involved in the process of bone metastasis from prostatic carcinoma.
人类前列腺癌常转移至骨组织，并在转移部位激活骨代谢，尤其是骨形成。据报道，前列腺癌提取物及源自骨转移病灶建立的人前列腺癌细胞系PC-3的条件培养基（CM）可刺激成骨细胞增殖。然而，关于PC-3 CM对成骨细胞分化的影响，相关信息较少。在本研究中，我们研究了PC-3 CM对两种成骨细胞分化的影响，一种是含有许多未分化骨祖细胞的原代胎鼠颅骨（RC）细胞，另一种是分化良好的大鼠骨肉瘤细胞系ROS 17/2.8。在第7、14和21天（RC细胞）或第3、6和9天（ROS 17/2.8细胞），PC-3 CM以剂量依赖方式（5%-30% CM）抑制骨结节形成及碱性磷酸酶（ALPase，一种成骨细胞标记酶）的活性。然而，该CM不影响细胞增殖或细胞活力。研究发现，PC-3 CM可显著阻断ALPase和骨钙素（OCN）mRNA的基因表达，但对骨桥蛋白（OPN）的mRNA表达无影响，后两者是与骨基质矿化相关的非胶原蛋白。这些发现表明，PC-3 CM含有一种抑制成骨细胞分化的因子，且该因子可能参与前列腺癌骨转移过程。
