Shih Lih-Yuann, Shih Hsin-Nung, Chen Tien-Hsiung
Department of Orthopedic Surgery, Chang-Gung Memorial Hospital, No 5, Fu-Hsing Street, Kwei-Shan, Tao-Yuan 333, Taiwan.
J Orthop Res. 2004 Nov;22(6):1161-7. doi: 10.1016/j.orthres.2004.03.004.
Production of bone resorption mediators and bone resorption activity were compared among osteolytic metastatic cancers, normal bone tissues, and soft tissue metastatic cancers to search for the possible factors leading to cancer-induced bone resorption. Twenty-five patients with untreated osteolytic metastatic breast or non-small cell lung cancers consisted of the study group. Normal bone tissues obtained from the same patient were used as internal controls; and tumor tissues from patients with soft tissue metastasis were used as external controls. Serum and urinary bone turnover markers were measured. Tissues harvested during surgery were subjected to tissue culture. The levels of prostaglandin E2 (PGE2), tumor necrosis factor-alpha (TNF-alpha), and interleukin-6 (IL-6) in the supernatant after 72 h of culture were measured. Bone resorption activity was measured by calcium release from cultured calvarias, and bone volume as well as osteoclast number in bone sections. Patients with osteolytic metastatic cancers showed significantly decreased serum osteocalcin, increased serum alkaline phosphatase, and urinary deoxypyridinoline levels. Osteolytic metastatic cancers produced significantly more PGE2 than both controls. Conditioned medium from osteolytic metastatic tumors showed significantly enhanced bone resorption activity, and indomethacin significantly reduced this activity. Levels of PGE2, and bone resorption activity increased in osteolytic tumor tissues than soft tissue metastatic tissues in the same patient indicated that the same tumor cells might respond differently to different microenvironments. Our observation showed that PGE2 was produced by osteolytic metastatic cancers and stimulated bone resorption in mice calvarias. PGE2 inhibitor may be applicable in reducing bone resorption by osteolytic metastatic cancers.
为了寻找导致癌症诱导骨吸收的可能因素，对溶骨性转移性癌症、正常骨组织和软组织转移性癌症的骨吸收介质产生及骨吸收活性进行了比较。研究组包括25例未经治疗的溶骨性转移性乳腺癌或非小细胞肺癌患者。从同一患者获取的正常骨组织用作内部对照；软组织转移患者的肿瘤组织用作外部对照。检测血清和尿骨转换标志物。手术中获取的组织进行组织培养。测量培养72小时后上清液中前列腺素E2（PGE2）、肿瘤坏死因子-α（TNF-α）和白细胞介素-6（IL-6）的水平。通过培养颅骨的钙释放、骨切片中的骨体积以及破骨细胞数量来测量骨吸收活性。溶骨性转移性癌症患者血清骨钙素显著降低，血清碱性磷酸酶升高，尿脱氧吡啶啉水平升高。溶骨性转移性癌症产生的PGE2显著多于两个对照组。溶骨性转移性肿瘤的条件培养基显示骨吸收活性显著增强，吲哚美辛显著降低这种活性。同一患者的溶骨性肿瘤组织中PGE2水平和骨吸收活性高于软组织转移性组织，表明相同的肿瘤细胞对不同的微环境可能有不同反应。我们的观察表明，PGE2由溶骨性转移性癌症产生并刺激小鼠颅骨的骨吸收。PGE2抑制剂可能适用于减少溶骨性转移性癌症引起的骨吸收。
