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Alendronate blocks metalloproteinase secretion and bone collagen I release by PC-3 ML cells in SCID mice

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Abstract

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

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  1. Department of Pathology, Allegheny University of the Health Sciences., Broad and Vine St., Philadelphia, PA, USA

    Mark E Stearns & Min Wang

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Stearns, M.E., Wang, M. Alendronate blocks metalloproteinase secretion and bone collagen I release by PC-3 ML cells in SCID mice. Clin Exp Metastasis 16, 693–702 (1998). https://doi.org/10.1023/A:1006524610591

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