Direct osteolysis induced by metastatic murine melanoma cells: Role of matrix metalloproteinases

We examined the osteolytic ability of metastatic cells and the role of tumour matrix metalloproteinases (MMPs) in bone degradation. The histomorphometry of experimental bone metastases of B16/F1 melanoma cells showed that osteolysis was associated with a 90% decrease in osteoclast number and predominance of cancer cells overlaying resorption pits. In vitro, B16/F1 cells and their conditioned medium (CM) degraded H-3-proline-labelled extracellular matrices from osteoblast-like cells and Ca-45-labelled calvariae. Using bone slices, we observed morphological evidence of degradation by B16/F1 cells. A role for tumour MMPs in bone degradation was supported by inhibition of degradation by 1,10-phenanthroline, collage I degradation by tumour cells and the presence of TPA-inducible M-r 90000, 84000 and 64000 gelatinolytic, and 54000 caseinolytic bands in B16/F1-CM. These studies indicate that metastatic cancer cells degrade bone matrix directly and that this is partially mediated by MMPs. (C) 1997 Published by Elsevier Science Ltd.