Alendronate blocks metalloproteinase secretion and bone collagen I release by PC-3 ML cells in SCID mice.
Alendronate blocks metalloproteinase secretion and bone collagen I release by PC-3 ML cells in SCID mice.
复制标题
阿仑膦酸钠可阻断 SCID 小鼠中 PC-3 ML 细胞的金属蛋白酶分泌和骨胶原 I 释放。
DOI：
10.1023/a:1006524610591
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发表时间：
1998
影响因子：
4
通讯作者：
Wang,M
中科院分区：
文献类型：
--
作者：
Stearns,ME;Wang,M
我们以前已经证明，阿仑膦酸盐，一种有效的二膦酸盐化合物，可以防止人PC-3 ML肿瘤细胞转移到骨（Stearns和Stearns，1996，Oncol Res，8，69-75）。本研究将肿瘤细胞在体内和体外分离后注入SCID小鼠股骨骨髓腔内。ELISA显示，骨髓（即在体外实验中）和血浆（即在体内实验中）中释放的胶原I的量是培养时间或股骨中注射的细胞数量的函数。ELISA还显示，股骨骨髓腔内分泌的基质金属蛋白酶（MMP-2和MMP-9）水平与胶原1的释放程度直接相关。用“活骨”和“灭活骨”进行的体外实验产生了类似的结果，表明肿瘤细胞（而不是破骨细胞）是观察到的骨溶解的主要原因。阿仑膦酸钠预处理SCID小鼠（0.1 mg/kg，每两周一次，持续3周）（或肿瘤细胞）阻断了肿瘤细胞（和破骨细胞）的MMP产生和胶原蛋白I的释放，提供了阿仑膦酸钠可用于预防转移性肿瘤细胞造成的骨破坏的直接证据。酶谱分析表明MMP-2的激活可能是骨溶解的原因。此外，数据表明，胶原蛋白I的血浆水平可能是骨转移和骨质溶解的标志物。
We have previously shown that alendronate, a potent bisphosphonate compound, can prevent human PC-3 ML tumor cell metastasis to the bone (Stearns and Stearns, 1996, Oncol Res, 8, 69-75). In this paper, tumor cells were injected into the bone medullary cavity of SCID mice femurs both in vivo and following isolation in vitro. ELISAs showed that the amount of collagen I released in the bone marrow (i.e. in in vitro experiments) and the blood plasma (i.e. in in vivo experiments) was a function of the time of incu-bation or the number of cells injected in the femurs. ELISAs also showed that the levels of matrix metal-loproteinase (MMP-2 and MMP-9) secreted in the bone medullary cavity of the femurs directly correlated with the extent of collagen 1 release. In vitro experiments carried out with ‘live’ and ‘devitalized bone’ yielded similar results suggesting that the tumor cells (not the osteoclasts) were primarily responsible for the bone solubilization observed. Alendronate pretreatment of the SCID mice (0.1 mg/kg biweekly for 3 weeks) (or the tumor cells) blocked both MMP production by the tumor cells (and the osteoclasts) and collagen I release, providing direct evidence that alendronate might be utilized to prevent bone destruction by metastatic tumor cells. Zymography indicated that MMP-2 activation might be responsible for bone solu-bilization. In addition, the data suggest that the plasma levels of collagen I might be a marker of bone metastasis and osteolysis.© Kluwer Academic Publishers 1998