The effect of Batimastat, a matrix metalloproteinase inhibitor, on experimental bone metastasis in an animal model

Thumbnail Image
Lee, Joanne Sung Yun
Journal Title
Journal ISSN
Volume Title
Skeletal metastases occur in $\sim$80% patients with advanced breast and prostate cancers. Despite the enormity of this problem, current therapies are generally directed at late stage lesions. An ideal treatment would prevent growth of micrometastatic cells and their effects on the host. Osteolysis is a dominant feature of bone metastases and can be mediated by tumor or host-derived matrix metalloproteinases (MMPs). Therefore, we have tested the hypothesis that Batimastat, an MMP inhibitor, will inhibit MMPs, osteolysis, and the development of experimental bone metastases by B16F1 murine melanoma cells and MDA-MB-231 human breast carcinoma cells. To test the effect of Batimastat on the growth of these cells, $4\times10\sp2$ tumor cells were grown in the presence of 0 $\mu$M to 50 $\mu$M Batimastat. To determine the effect of Batimastat in vivo, $1\times10\sp5$ B16F1 and MDA-MB-231 cells were injected into the systemic arterial circulation of C57bl/6 and BalbC nu/nu mice. Some groups were also treated with Batimastat at 30 mg/Kg i.p. Histomorphometry was performed 15 and 21 days later to evaluate the formation of metastatic bone tumors in the vertebrae and metaphyseal regions of long bone. (Abstract shortened by UMI.)