title: Direct osteolysis induced by metastatic murine melanoma cells: role of matrix metalloproteinases.
abstract: 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.
authors.affiliation: Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
authors.forename: O H
authors.initials: OH
authors.lastname: Sanchez-Sweatman
authors.forename: J
authors.initials: J
authors.lastname: Lee
authors.forename: F W
authors.initials: FW
authors.lastname: Orr
authors.forename: G
authors.initials: G
authors.lastname: Singh
mesh_terms: D000818:Animals; D001857:Bone Matrix / Q000378:metabolism; D001859:Bone Neoplasms / Q000378:metabolism / Q000556:secondary*; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D008546:Melanoma, Experimental / Q000150:complications* / Q000378:metabolism; D008666:Metalloendopeptidases / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D010014:Osteolysis / Q000209:etiology* / Q000378:metabolism; D012878:Skin Neoplasms / Q000150:complications* / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D003094:Collagen; D008666:Metalloendopeptidases