Yonou Hiroyuki, Ochiai Atsushi, Goya Masato, Kanomata Naoki, Hokama Sanehiro, Morozumi Makoto, Sugaya Kimio, Hatano Tadashi, Ogawa Yoshihide
Department of Urology, University of the Ryukyus, Nishihara, Okinawa, Japan.
Prostate. 2004 Mar 1;58(4):406-13. doi: 10.1002/pros.10349.
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.
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.
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.
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.
超过80%的晚期前列腺癌患者发生骨转移，但骨转移的生物学机制尚不清楚。本研究在尽可能接近人类骨环境的条件下，研究骨转移瘤的体内形成和进展情况。
将成人骨碎片皮下植入120只雄性NOD/SCID小鼠体内。四周后，分别向80只或40只小鼠静脉注射1×10⁷个LNCaP前列腺癌细胞或磷酸盐缓冲盐水。注射后2、4、6和8周，每组分别从20只至10只小鼠体内取出植入的骨碎片。
LNCaP细胞在2周内定植于骨髓血管，然后逐渐扩展至整个髓腔。成骨反应常发生在转移灶边缘（小梁间骨化生）。此外，在成熟板层骨旁观察到新骨形成（贴壁性骨形成）。这两个过程似乎通过不同机制发生，但可能同样导致骨硬化。破骨细胞在肿瘤早期侵袭部位数量显著增加，而在肿瘤侵袭完全的部位则很少观察到破骨细胞。
伴有吸收的成骨改变占优势可能导致转移灶中的骨重塑，破骨细胞可能在前列腺癌骨转移中起重要作用。
