Peterschmitt J, Bäuerle T, Berger MR.
Clin Exp Metastasis. 2007;24(6):449-59. Epub 2007 Jul 18.
Toxicology and Chemotherapy Unit, Deutsches Krebsforschungszentrum Heidelberg, Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.
The aim of this study was to investigate the combined effect of zoledronic acid and an antibody against bone sialoprotein II (BSPII) on proliferation and osteolytic activity of MDA-MB-231(GFP) breast cancer cells. For this purpose, the cells were exposed to zoledronic acid (10-20 microg/ml [25-50 microgM]) and an anti-BSPII IgY (10-100 microg/ml) for up to 5 days alone or in combination. The combined treatment showed synergistic antiproliferative effects at the higher dose of zoledronic acid. Following inoculation of 1 x 10(5) MDA-MB-231 (GFP) breast cancer cells into a branch of the femoral artery of nude rats, lytic lesions developed in the tibia, femur or fibula of the injected hind leg after approximately 30 days. The appearance and development of these lesions were monitored radiographically. Rats with lytic lesions were treated with zoledronic acid (60 microg/kg/week sc x 8; n = 10), zoledronic acid and an anti-BSPII IgY antibody (60 microg/kg/week sc x 8 + 10 mg/kg/week sc x 8; n = 10), or left untreated (n = 20). In addition, rats were treated for 4 weeks (n = 10) with both regimens starting right after tumor cell inoculation. Finally, ten rats were treated with zoledronic acid for 2 weeks before tumor cell inoculation (60 microg/kg/week sc x 2). The antiosteolytic effect of zoledronic acid was high as shown by inhibition of osteolytic growth. Addition of the anti-BSPII IgY further decreased the incidence of femoral osteolytic lesions (40% reduction), indicating remineralization, and reduced periosteal defects of cortical bone (20% reduction). These observations favor using the IgY-antibody in addition to zoledronic acid in order to stimulate osteoblast-induced remineralization.