Periosteal and intratumorous bone formation in athymic nude mice by Chinese hamster ovary tumors expressing murine bone morphogenetic protein-4.
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.
Shimizu
K
K
Department of Orthopedic Surgery, Osaka University Medical School, Japan.
Yoshikawa
H
H
Matsui
M
M
Masuhara
K
K
Takaoka
K
K
D000818:Animals; D001846:Bone Development / Q000187:drug effects*; D019485:Bone Morphogenetic Proteins; D006224:Cricetinae; D003412:Cricetulus; D004270:DNA, Circular; D005260:Female; D006133:Growth Substances / Q000494:pharmacology*; D051379:Mice; D008819:Mice, Nude; D009363:Neoplasm Proteins / Q000494:pharmacology; D012516:Osteosarcoma / Q000648:ultrastructure; D010053:Ovary / Q000166:cytology; D010521:Periosteum / Q000648:ultrastructure; D011506:Proteins / Q000235:genetics / Q000494:pharmacology*; D012513:Sarcoma, Experimental; D014162:Transfection
D019485:Bone Morphogenetic Proteins; D004270:DNA, Circular; D006133:Growth Substances; D009363:Neoplasm Proteins; D011506:Proteins