Treatment of bone metastasis induced by MDA-MB-231 breast cancer cells with an antibody against bone sialoprotein.
The extracellular bone matrix protein bone sialoprotein (BSP) is considered to play an important role in the pathogenesis of lytic skeletal lesions which are associated with severe morbidity in breast, prostate or lung cancer patients. In addition to in vitro studies, nude rats were implanted with 10(5) MDA-MB-231 cells transfected with GFP into a small branch of the femoral artery. Osteolytic lesions of the respective hind leg were detected by X-ray and CT analysis as well as by immunohistochemistry. Exposure of MDA-MB-231GFP cells in vitro to an antibody against BSP (0-400 microg/ml) decreased proliferation, colony formation and migration of these cells by up to 95, 83 and 89 T/C%, respectively. In nude rats, pre-incubation of MDA-MB-231GFP cells prior to inoculation (25-100 microg/ml) reduced the mean osteolytic lesion size to 22 T/C% after 90 days of observation (p<0.05). Treatment of overt lytic metastasis with the anti-BSP antibody (10 mg/kg) resulted in a significantly smaller mean lesion size of 57 T/C% at the end of the observation period (p<0.05) as well as in new bone formation. Immunohistochemical analysis revealed the presence of BSP in MDA-MB-231GFP cells and in vessel endothelium cells during processes such as migration and invasion. In conclusion, an anti-BSP antibody decreased proliferation, colony formation and migration of MDA-MB-231GFP cells in vitro and reduced osteolysis besides inducing bone formation in a nude rat model.
Bäuerle
Tobias
T
Unit of Toxicology and Chemotherapy, Deutsches Krebsforschungszentrum Heidelberg, 69120 Heidelberg, Germany.
Peterschmitt
Jenny
J
Hilbig
Heidegard
H
Kiessling
Fabian
F
Armbruster
Franz P
FP
Berger
Martin R
MR
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000556:secondary; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002645:Chickens; D004305:Dose-Response Relationship, Drug; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000276:immunology / Q000494:pharmacology / Q000627:therapeutic use; D058574:Integrin-Binding Sialoprotein; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology; D008856:Microscopy, Fluorescence; D051381:Rats; D011923:Rats, Nude; D012795:Sialoglycoproteins / Q000276:immunology*; D013997:Time Factors; D014057:Tomography, X-Ray Computed; D014162:Transfection; D014410:Tumor Stem Cell Assay; D023041:Xenograft Model Antitumor Assays / Q000379:methods
D000911:Antibodies, Monoclonal; C546871:IBSP protein, human; C546873:Ibsp protein, rat; C016512:IgY; D007136:Immunoglobulins; D058574:Integrin-Binding Sialoprotein; D012795:Sialoglycoproteins; D049452:Green Fluorescent Proteins