Breast cancer cells (BCC) frequently metastasize to bone where they may cause tumor-induced osteolysis (TIO). While the important eroding role of the osteoclasts in TIO has been recognized, the possibility that BCC and/or osteoblasts activated by tumoral factors could also directly degrade bone matrix in this pathology has been less investigated. We show here that the net collagen amounts produced in vitro by human osteoblasts and osteoblast-like cells (SaOS-2, MG-63) were significantly reduced by culture medium conditioned by several BCC lines (T-47D, MDA-MB-231, IBEP-1, IBEP-2, IBEP-3). There was no evidence for a decrease in collagen synthesis, as assessed by the production of the carboxyterminal propeptide of type I collagen. In contrast, the effect of BCC-derived medium on collagen amounts was attenuated by inhibitors of matrix metalloproteinases (MMPs) as well as by tranexamic acid, an inhibitor of the plasminogen conversion to plasmin, while it was abolished in presence of the two kinds of proteinase inhibitors. This osteoblastic protein degradation activity appeared to be attributable to factors secreted by the osteoblasts as well as by the BCC. These factors have molecular weights lower as well as higher than 10 kD. Our data suggest that besides the eroding action of the osteoclasts, BCC- and osteoblasts-derived MMPs and serine proteinases might play a direct role in the reduction of bone collagen, which is a hallmark of TIO.
