Intraosseous growth of human prostate cancer in implanted adult human bone: Relationship of prostate cancer cells to osteoclasts in osteoblastic metastatic lesions
Intraosseous growth of human prostate cancer in implanted adult human bone: Relationship of prostate cancer cells to osteoclasts in osteoblastic metastatic lesions
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DOI：
10.1002/pros.10349
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发表时间：
2004-03-01
期刊：
影响因子：
2.8
通讯作者：
Ogawa, Y
中科院分区：
文献类型：
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作者：
Yonou, H;Ochiai, A;Ogawa, Y
背景超过80%的晚期前列腺癌患者有骨骼受累，但对骨转移的生物学知之甚少。本研究在尽可能接近人体骨环境的条件下研究骨转移瘤的体内形成和进展。将成人骨碎片皮下植入120只雄性NOD/SCID小鼠。四周后，分别将1 × 10（7）LNCaP前列腺癌细胞或磷酸盐缓冲盐水静脉注射到80或40只小鼠中。分别于注射后2、4、6、8周从每组20 ~ 10只小鼠体内取出植入的骨碎片。LNCaP在2周内定殖于骨髓血管，然后逐渐扩展到整个髓腔。成骨细胞反应通常发生在转移灶的边缘（小梁间骨化生）。此外，在成熟板层骨附近观察到新骨形成（贴壁骨形成）。这两个过程似乎通过不同的机制发生，但可能类似地导致骨质疏松症。破骨细胞在肿瘤早期浸润的部位数量明显增加，而在肿瘤完全浸润的部位几乎没有破骨细胞。成骨细胞的优势变化与吸收可能导致骨重建的转移病灶，破骨细胞可能在前列腺癌骨转移中发挥重要作用。(C)2003 Wiley-Liss，Inc.
BACKGROUND. More than 80% of patients with advanced prostate cancer have skeletal involvement, but the biology of bone metastasis is poorly understood. This study investigated the in vivo formation and progression of bone metastases under conditions that resembled the human bone environment as closely as possible.METHODS. Adult human bone fragments were implanted subcutaneously into 120 male NOD/SCID mice. Four weeks later, 1 X 10(7) LNCaP prostate cancer cells or phosphate-buffered saline were injected intravenously into 80 or 40 mice, respectively. The implanted bone fragments were removed from 20 to 10 mice in each group at 2,4, 6, and 8 weeks after injection.RESULTS. LNCaP colonized the bone marrow blood vessels within 2 weeks, and then gradually expanded into the entire medullary cavity. An osteoblastic response often occurred at the edges of metastatic foci (intertrabecular bone metaplasia). In addition, new bone formation was observed adjacent to mature lamellar bone (appositional bone formation). These two processes appeared to occur through different mechanisms, but might similarly cause osteosclerosis. Osteoclasts showed a marked increase in numbers at sites of early tumor invasion, whereas few osteoclasts were observed at sites where tumor invasion was complete.CONCLUSIONS. The predominance of osteoblastic change with resorption may lead to bone remodeling in metastatic lesions, and osteoclasts may play an important role in bone metastasis from prostate cancer. (C) 2003 Wiley-Liss, Inc.