Saito Hidemi, Tsunenari Toshiaki, Onuma Etsuro, Sato Koh, Ogata Etsuro, Yamada-Okabe Hisafumi
Pharmaceutical Research Department III, Kamakura Research Laboratories, Chugai Pharmaceutical Co., Ltd., Kamakura, Kanagawa 247-8530, Japan.
Anticancer Res. 2005 Nov-Dec;25(6B):3817-23.
Parathyroid hormone-related protein (PTHrP) has been implicated in bone metastasis. However, the effects on bone metastasis of blocking the PTHrP function have not been tested in the clinic. Here, the effects of a humanized anti-PTHrP monoclonal antibody (mAb) on bone metastasis in a human xenograft model are shown.
Subline MDA-5a, with high bone metastatic activity, was established from the human breast cancer cell line MDA-MB-231. Mice were injected with MDA-5a and an anti-PTHrP monoclonal antibody (mAb) raised against human PTHrP (1-34); bone metastasis was evaluated by X-ray photography.
MDA-5a produced elevated levels of PTHrP, Interleukin 8 (IL-8), IL-6 and matrix metalloproteinase 1 (MMP-1) and frequently metastasized to the bone. Administration of the humanized anti-PTHrP mAb significantly suppressed osteolytic bone metastasis of MDA-5a and caused osteogenesis at the sites of metastasis.
The humanized anti-PTHrP mAb was effective against bone metastasis by inducing osteogenesis and, therefore, will provide a new treatment option for bone metastasis in breast cancer.
甲状旁腺激素相关蛋白（PTHrP）与骨转移有关。然而，阻断PTHrP功能对骨转移的影响尚未在临床上得到验证。在此，展示了一种人源化抗PTHrP单克隆抗体（mAb）对人异种移植模型中骨转移的影响。
从人乳腺癌细胞系MDA-MB-231中建立具有高骨转移活性的亚系MDA-5a。给小鼠注射MDA-5a和一种针对人PTHrP（1-34）产生的抗PTHrP单克隆抗体（mAb）；通过X线摄影评估骨转移情况。
MDA-5a产生高水平的PTHrP、白细胞介素8（IL-8）、IL-6和基质金属蛋白酶1（MMP-1），并经常转移至骨。给予人源化抗PTHrP单克隆抗体可显著抑制MDA-5a的溶骨性骨转移，并在转移部位诱导成骨。
人源化抗PTHrP单克隆抗体通过诱导成骨对骨转移有效，因此将为乳腺癌骨转移提供一种新的治疗选择。
