Dohi Osamu, Hatori Masahito, Suzuki Takashi, Ono Katsuhiko, Hosaka Masami, Akahira Jun-ichi, Miki Yasuhiro, Nagasaki Shuji, Itoi Eiji, Sasano Hironobu
Department of Orthopaedic Surgery, Tohoku Kosai Hospital, 2-3-11 Kokubuncho, Aoba-ku, Sendai, Japan.
Cancer Sci. 2008 Mar;99(3):518-23. doi: 10.1111/j.1349-7006.2007.00673.x. Epub 2007 Dec 15.
Sex steroid receptors including estrogen receptors (ER), progesterone receptors (PR), and androgen receptors (AR) have been sporadically reported in human osteosarcoma or its cell lines. Therefore, sex steroids have been considered to play some roles in human osteosarcoma, but no systematic and detailed studies regarding the correlation between the status of these receptors in sarcoma cells and clinicopathological parameters have been reported. We examined the existence of ER, PR and AR in 28 cases of osteosarcoma using immunohistochemistry. We then characterized the potential influence of sex steroids on cell proliferation of osteosarcoma cells using MG-63 human osteosarcoma cell line, which expressed all of these receptors. ER-beta and PR were detected in the great majority of the cases (23 and 24 cases, respectively) but ER-alpha and aromatase were not detected in all the cases, and AR was detected only in eight cases. There was a significant positive correlation between ER-beta and Ki-67 (MIB1) labeling indexes. The absence of aromatase in tumors also suggests the relative importance of concentrations of circulating sex steroids. Proliferation of MG-63 cells was significantly stimulated by estradiol, progesterone, and 5 alpha-dihydrotestosterone (DHT), and was significantly suppressed by the addition of fulvestrant (ICI), mifepristone (RU), and hydroxiflutamide, blockers for ER, PR and AR, respectively. Sex steroids, particularly estrogen and progesterone, are considered to play important roles in the regulation of cell proliferation in human osteosarcoma. In addition, these data suggest the potential for a novel endocrine therapy in osteosarcoma using clinically available inhibitors of progesterone and estrogen actions.
包括雌激素受体（ER）、孕激素受体（PR）和雄激素受体（AR）在内的性类固醇受体已在人类骨肉瘤或其细胞系中被零星报道。因此，性类固醇被认为在人类骨肉瘤中发挥一定作用，但尚未有关于肉瘤细胞中这些受体状态与临床病理参数之间相关性的系统而详细的研究报道。我们采用免疫组织化学方法检测了28例骨肉瘤中ER、PR和AR的存在情况。然后，我们使用表达所有这些受体的MG-63人骨肉瘤细胞系，研究了性类固醇对骨肉瘤细胞增殖的潜在影响。在绝大多数病例中检测到了ER-β和PR（分别为23例和24例），但并非所有病例都检测到ER-α和芳香化酶，仅在8例中检测到AR。ER-β与Ki-67（MIB1）标记指数之间存在显著正相关。肿瘤中缺乏芳香化酶也提示了循环性类固醇浓度的相对重要性。雌二醇、孕酮和5α-二氢睾酮（DHT）显著刺激MG-63细胞增殖，而分别添加氟维司群（ICI）、米非司酮（RU）和羟基氟他胺（ER、PR和AR的阻滞剂）则显著抑制其增殖。性类固醇，尤其是雌激素和孕酮，被认为在人类骨肉瘤细胞增殖的调节中起重要作用。此外，这些数据提示了使用临床上可用的孕酮和雌激素作用抑制剂对骨肉瘤进行新型内分泌治疗的可能性。
