H-31 human breast cancer cells stimulate type I collagenase production in osteoblast-like cells and induce bone resorption.
Bone is one of the most common sites of metastasis in breast cancer. For metastasis to occur in bone, tumor cells must induce osteolysis by osteoclasts. Degradation of the osteoid layer by type I collagenase is a necessary process before osteolysis can occur because the osteoid layer hinders osteoclasts from adhering to bone. In this study, we investigated the function of H-31 human breast cancer cells in inducing type I collagenase production and in enhancing bone resorption. H-31 cells did not themselves produce type I collagenase whereas MG-63 human osteoblast-like cells and MC3T3-E1 mouse osteoblast cells constantly produced type I collagenase. When these osteoblast-like cells were cocultured with H-31 cells, type I collagenase production was enhanced. The same enhancement occurred when the conditioned medium of H-31 cells was added to the osteoblast-like cells. The activity of this type I collagenase was inhibited by EDTA and minocyclin, an inhibitor of matrix metalloproteinases, hence it was identified as matrix metalloproteinase-1 (MMP-1). H-31 cells exhibited chemotactic migration towards collagen; therefore, collagen degraded by MMP-1 may play an important role in the localisation of breast cancer cells like H-31 to bone. In an organ culture system using newborn mouse calvaria, the conditioned medium of H-31 cells increased the concentration of calcium in the medium, and this effect was inhibited by minocyclin, indicating that bone resorption occurred in this system. Based on these observations, we speculate that type I collagenase produced by osteoblast cells in response to breast cancer cells (exemplified by H-31) may facilitate degradation of the osteoid layer and the homing of breast cancer cells to bone. This can lead to osteolysis by osteoclasts, a crucial event for bone metastasis.
Ohishi
K
K
Institute of Molecular and Cellular Biosciences, University of Tokyo, Japan.
Fujita
N
N
Morinaga
Y
Y
Tsuruo
T
T
D001862:Bone Resorption / Q000201:enzymology* / Q000209:etiology*; D001842:Bone and Bones / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D002118:Calcium / Q000378:metabolism; D002633:Chemotaxis; D003094:Collagen / Q000494:pharmacology; D017364:Collagenases / Q000096:biosynthesis* / Q000378:metabolism; D017077:Culture Media, Conditioned; D006801:Humans; D010006:Osteoblasts / Q000201:enzymology*; D010446:Peptide Fragments / Q000502:physiology; D014407:Tumor Cells, Cultured
D017077:Culture Media, Conditioned; D010446:Peptide Fragments; D003094:Collagen; D017364:Collagenases; D002118:Calcium