Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A cDNA clone encoding bone morphogenetic protein-4 (BMP-4) has been isolated from a human placental cDNA library. Sequence analysis of this clone revealed that the nucleotide sequence of 5' region was different from that of human osteosarcoma BMP-4 and the deduced amino acid sequence indicated deletion of N-terminal 6 amino acids. We confirmed the expression of this type of BMP-4 mRNA in one human osteogenic cell line in addition to the placenta by the polymerase chain reaction (PCR).
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PMID:Cloning and sequence of bone morphogenetic protein 4 (BMP-4) from a human placental cDNA library. 757 80

Periosteal sunburst spiculation is a peculiar radiographic feature of osteosarcoma, and it represents a reactive ossification resulting from the action of normal osteoblasts rather than tumor cells. Because bone morphogenetic protein is known to be a potent inducer of ectopic bone formation, the authors hypothesized that bone morphogenetic protein may be involved in the pathogenesis of such reactive bone formation in osteosarcoma. Chinese hamster ovary cells transfected with the bone morphogenetic protein-4 gene were injected into the femurs of athymic nude mice to form experimental bone tumors producing bone morphogenetic protein. Two weeks after intramedullary injection, new bone formation was observed radiographically and histologically within the extraosseous portions of the tumors. This showed a close resemblance to sunburst spiculation in human osteosarcomas. In contrast, the control nontransformed Chinese hamster ovary tumors showed no extraosseous bone formation. Because the induced bone was composed of multiple parallel spicules similar to those found in human bone morphogenetic protein-producing osteosarcomas, these findings suggest that periosteal sunburst spiculation may be the result of bone morphogenetic protein production by osteosarcoma cells.
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PMID:Periosteal sunburst spiculation in osteosarcoma. A possible role for bone morphogenetic protein. 795 86

To determine whether a system of ectopic bone formation induced by osteosarcoma-derived bone-inducing substance (bone morphogenetic protein-4) can be used as a model of developing bone at the molecular level, we studied the expression of bone-related protein mRNAs in the process of ectopic bone formation using non-radioisotopic in situ hybridization. Osteonectin mRNA was detected in fibroblast-like cells, which are similar to periosteal cells from the early to middle stages of bone development. The proportion of osteonectin mRNA-expressing cells was greater than that of osteopontin mRNA-expressing cells in hypertrophic chondrocytes and osteoblast-like cells. In contrast, osteopontin mRNA was localized in a limited population of hypertrophic chondrocytes, a single layer of osteoblast-like cells adjacent to the bone trabeculae in the middle stage of bone formation, and in a limited subset of osteocytes in the late stage. A strong osteocalcin mRNA signal was detected in osteoblast-like cells from the middle to late stages and in a limited subset of osteocytes in the late stage of bone development. Since the sequential gene expression pattern of bone-related proteins in the present system is comparable to that in embryonic osteogenesis, this system may be useful as a model for studying gene expression in osteogenesis.
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PMID:Expression of mRNA of murine bone-related proteins in ectopic bone induced by murine bone morphogenetic protein-4. 805 37

This study was undertaken to identify the factor responsible for classical transfilter bone induction by a murine osteosarcoma. Chinese hamster ovary (CHO) cells were transfected with the complementary DNA (cDNA) for bone morphogenetic protein-4 (BMP-4) that was purified from a murine (Dunn) osteosarcoma. Diffusion chambers were filled with the cells expressing the gene for BMP-4 and implanted subcutaneously into the flanks of ICR strain nude mice. Ectopic transfilter bone formation was seen consistently on the outer surfaces of the cellulose acetate membranes of chambers containing transfected cells at three weeks after implantation. Bone was not observed on chambers loaded with nontransfected CHO cells. The transfected CHO cells were inoculated into nude mice to form tumors, which were then homogenized, defatted, and bioassayed also in the ICR, nu/nu mice. The cell-free implants consistently elicited new bone and marrow within three weeks, whereas the control implants consisting of nontransfected tumor were not osteoinductive. These experimental results suggest that BMP-4 is one of the molecules responsible for the transfilter bone induction by vital Dunn osteosarcoma cells reported by Heiple and for the ectopic bone induction after implantation of devitalized, freeze-dried Dunn osteosarcoma tissue described originally by Amitani.
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PMID:Transfilter bone induction by Chinese hamster ovary (CHO) cells transfected by DNA encoding bone morphogenetic protein-4. 813 48

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.
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PMID:Periosteal and intratumorous bone formation in athymic nude mice by Chinese hamster ovary tumors expressing murine bone morphogenetic protein-4. 813 49

Based on information from partial amino acid sequences of a protein with bone-inducing activity that was purified from a murine osteosarcoma (Dunn type), a cDNA library of the sarcoma was screened to clone a gene complementary to the protein. The cloned cDNA was amplified and transfected into Chinese hamster ovarian (CHO) cells for expression. When the protein produced by the transfected cell line was implanted in combination with pure carrier collagen into allogeneic mice, ectopic ossicles consistently developed at implanted sites within two weeks. The nucleotide sequence of the cDNA and its deduced amino acid sequence were homologous to those of human bone morphogenetic protein-4 (also BMP-2B). In addition, the cDNA and deduced amino acid sequences were identical to those proposed for murine BMP-4 derived from the normal murine fetus. It is postulated that the cloned cDNA encodes the protein responsible for bone formation induced by implantation of devitalized Dunn-type osteosarcoma tissue or cells. The protein product was identified as murine BMP-4, a member of the TGF-beta gene family.
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PMID:Gene cloning and expression of a bone morphogenetic protein derived from a murine osteosarcoma. 835 41

Protein-independent cells are useful for analysis of proteins that are produced by the cells themselves without any consideration of exogenous proteins. This experimental protein-independent tumor system provides new biology of the autonomous nature of neoplastic cells during their evolution. We established a Dunn protein-free osteosarcoma (DPF) cell line, which was derived from parental fetal calf serum (FCS)-dependent murine Dunn osteosarcoma (DOS) cells. The DPF cells grew in a chemically defined protein-free medium at the high seeding density of 1x10(4) cells/well of a 96-well-plate with a similar doubling time to that of cells growing in the presence of FCS, while the cells did not grow at a density lower than 1x10(3)/well. Furthermore, addition of conditioned medium stimulated the growth in a dose-dependent manner. In contrast, DOS did not grow in the protein-free condition at all. Morphological examination revealed that DPF cells exhibited a more round shape than DOS cells. RT-PCR analysis exhibited the augmentation of the RNA message of bone morphogenetic protein-4 (BMP-4) and osteocalcin in DPF cells. Enhanced expression of BMP-4 protein was also demonstrated by immunoblot analysis. Furthermore, alkaline phosphatase (ALP) activity was higher in DPF cells, indicating that bone-formation related molecules may be overexpressed in protein-independent osteosarcoma cells. These results suggest that putative growth factors may play a role in the DPF cell growth in an autocrine fashion, and the acquisition of autonomous growth independent of exogenous proteins may be coupled to the osteogenic differentiation.
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PMID:Expression of bone formation-related molecules in a newly established protein-independent osteosarcoma. 1135 Dec 51