Bone morphogenetic protein-2 and tumor growth: Diverse effects and possibilities for therapy.

Concern regarding safety with respect to the clinical use of human bone morphogenetic protein-2 (BMP-2) has become an increasingly controversial topic. The role of BMP-2 in carcinogenesis is of particular concern. Although there have been many studies of this topic, the results have been contradictory and confusing. We conducted a systematic review of articles that are relevant to the relationship or effect of BMP-2 on all types of tumors and a total of 97 articles were included. Studies reported in these articles were classified into three major types: "expression studies", "in vitro studies", and "in vivo studies". An obvious pattern was that those works that hypothesize an inhibitory effect for BMP-2 most often examined only the proliferative properties of the tumor cells. This subset of studies also contained an extraordinary number of contradictory findings which made drawing a reliable general conclusion impossible. In general, we support a pro-tumorigenesis role for BMP-2 based on the data from these in vitro cell studies and in vivo animal studies, however, more clinical studies should be carried out to help make a firm conclusion.