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 n ormal osteoblasts. BMP-2 is structurally related to transforming growt h 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 recombi nant human BMP-2 (rhBMP-2) can modulate the proliferation of human tum or colony-forming units taken from 113 patients. Tumor cells were cult ured 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 prolif eration. A significant inhibition (50% or less survival of tumor colon y-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 t umors and two of 15 ovarian tumors. A concentration-response relations hip was observed (p < 0.001 by Mantel-extension test). The results of this study encourage further evaluation of the antiproliferative effec ts of rhBMP-2 against human cancers. [(C) 1998 Lippincott-Raven Publis hers.].