Periosteal and Intratumorous Bone Formation in Athymic Nude Mice by Chinese Hamster Ovary Tumors Expressing Murine Bone Morphogenetic Protein-4

Abstract

Chinese hamster ovary (CHO) cells were transfected with the complementary DNA (cDNA) for bone morphogenetic protein-4 (BMP-4) that was derived from the poly A-RNA of a murine (Dunn) osteosarcoma. A clonal line of the transfected, BMP-4 gene expressing cells was expanded and inoculated into the hindlimbs of nude mice to produce BMP-4 secreting tumors. The aims of this study were to investigate the systemic effects of endogenous BMP-4 production on skeletal growth and radiologic density, the local effects of BMP-4 on bone at the tumor-bone interface, and the changes in tumor histology as a result of transfecting CHO cells with the gene for BMP-4. In control mice, mock vector-transfected CHO cells were inoculated in the same manner. Three weeks after the mice received the transfected cells, neither enhanced skeletal growth nor a change in bone density was noted. However, at the site where the bone was in contact with the tumor, new cartilage and bone were consistently observed. The murine BMP-4 transfected CHO tumor contained spicules of new bone that have been described as a histologic feature characteristic of osteosarcoma.