Direct osteolysis induced by metastatic murine melanoma cells: Role of matrix metalloproteinases
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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 3H-proline-labelled extracellular matrices from osteoblast-like cells and 45Ca-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, collagen I degradation by tumour cells and the presence of TPA-inducible M(r) 90,000, 84,000 and 64,000 gelatinolytic, and 54,000 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.
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