Antiproliferative effects of recombinant human bone morphogenetic protein-2 on human tumor colony-forming units.
Bone morphogenetic protein-2 (BMP-2) is a differentiation factor for normal osteoblasts. BMP-2 is structurally related to transforming growth factor-beta which inhibits cell proliferation and enhances apoptosis. A recent study has shown the presence of BMP-2 receptors on several cancer cell lines. In this study, we attempted to determine if recombinant human BMP-2 (rhBMP-2) can modulate the proliferation of human tumor colony-forming units taken from 113 patients. Tumor cells were cultured in soft agar and continuously exposed to three concentrations of rhBMP-2 (10, 100 and 1000 ng/ml) for 14 days in the capillary cloning system. There were 65 evaluable specimens, including 17 breast cancers, 15 ovarian cancers, 14 non-small cell lung cancers and five prostate cancers. Importantly, rhBMP-2 did not stimulate the tumor cell proliferation. A significant inhibition (50% or less survival of tumor colony-forming units) was seen in 16 of 65 specimens (24.6%) at 1000 ng/ml, including five of 14 non-small cell lung cancers, five of 17 breast tumors and two of 15 ovarian tumors. A concentration-response relationship was observed (p<0.001 by Mantel-extension test). The results of this study encourage further evaluation of the antiproliferative effects of rhBMP-2 against human cancers.
Soda
H
H
Translational Research Laboratory, Institute for Drug Development, Cancer Therapy and Research Center, San Antonio, TX 78229, USA.
Raymond
E
E
Sharma
S
S
Lawrence
R
R
Cerna
C
C
Gomez
L
L
Timony
G A
GA
Von Hoff
D D
DD
Izbicka
E
E
D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D011994:Recombinant Proteins / Q000633:toxicity; D016212:Transforming Growth Factor beta; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; C499469:recombinant human bone morphogenetic protein-2