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Query: UMLS:C0029463 (osteosarcoma)
 16,637 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The morphology of 26 cases of osteogenic sarcoma was studied using electron microscopic techniques, and the localization of acid and alkaline phosphatase activity at the ultrastructural level elucidated. Four different cells were present in the tumours: osteoblast-like, fibroblast-like, chondroblast-like, and multinucleated giant cells. The osteoblast-like cell was present in most of the tumours studied. Acid phosphatase activity was present in lysosome-like structures of almost all the cell-types studied. Alkaline phosphatase activity was noted in or on the plasma membranes and associated vesicles of osteoblast-like, fibroblast-like, and multinucleated giant cells. The abundant reaction product deposition of alkaline phosphatase as compared with the lower acid phosphatase activity is in agreement with the nature of this bone-forming tumour. The results of the histochemical studies have added to the understanding of the pathobiology of the different cells composing osteogenic sarcomas.
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PMID:Human osteogenic sarcoma. Study of the ultrastructure, with special notes on the localization of alkaline and acid phosphatase. 696 89

Thirty cases of human osteosarcoma were transplanted subcutaneously in BALB/c nude mice. Twenty-four tumours survived in animals and showed the histopathology of the original tumours. Growth of transplantable tumours was closely related to the amount of osteoid tissue and tumours with predominant osteoid tissue showed slow growth. Tumours whose osteoid-forming activity tended to diminish or disappear were likely to fail early during serial transplantation. Two osteosarcoma (SU and ISHI) were established into permanent transplantable strains and were maintained in nude mice for more than three years. These two strains showed striking differences in their growth capacity; SU grew rapidly and frequently formed pulmonary tumours after tail vein injection of tumour cells. Histologically, ISHI osteosarcoma cells continue to form osteoid tissue, whereas SU cells showed anaplastic changes and lost osteoid-forming activity. Alkaline phosphatase and Lactate Dehydrogenase (LDH) activities of tumour tissue were lower in ISHI than SU, and significant elevation of the relative value of Fraction III of LDH isozyme has been demonstrated in SU, and Fraction IV in ISHI. On this basis, the authors discuss the relation between the amount of osteoid formation or LDH isozyme patterns and the malignant potential of human osteosarcoma.
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PMID:Analysis of osteoid-forming activity of human osteosarcoma implanted into nude mice. 696 45

A cartilaginous tumor derived from a human osteogenic sarcoma of the mandible has been maintained by serial passage to nude mice. Tumor growth was multilobular. Radiopaque spots were seen scattered throughout the tumor at three months after transplantation. Both light and electron microscopic examination at three months revealed that the tumor contained cartilaginous cells at various stages of differentiation. There was metachromasia throughout tumor lobules except in the marginal region. Von Kossa staining was positive in the central region. Ultrastructural study identified four subtypes of chondrocytic cells of a neoplastic nature. In the extracellular matrix around hypertrophic cells, matrix vesicles were observed with mineral deposits. Alkaline phosphatase was found on the plasma membrane and Golgi complexes of hypertrophic cells, and on matrix vesicles. Thus cell lineage and the manner of calcification of the transplanted tumor were similar to those of epiphyseal growth cartilage.
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PMID:Biological and morphological characteristics of a transplanted cartilaginous tumor derived from a human osteogenic sarcoma. 752 50

Human osteosarcoma and fibrosarcoma cell lines were investigated for alterations in oncogenes, tumor suppressor genes, and growth factors, all of which have been implicated in tumor formation. Characterization of oncogenes that are involved in osteosarcoma formation, including the c-fos and c-myc oncogenes, indicated that all six osteosarcoma cell lines examined had 5- to 20-fold amplification of the c-myc oncogene, whereas neither of two fibrosarcoma cell lines c-myc amplification. Interestingly, only three of six osteosarcoma cell lines displayed altered c-myc immediate-early gene function. c-fos was found to be normal, both at the gene and functional levels, in all six osteosarcoma and both fibrosarcoma cell lines tested. Characterization of two tumor suppressor genes, p53 and RB1, that have been implicated in osteosarcoma formation indicated that p53 was altered in five of six osteosarcoma cell lines, whereas RB1 was altered in only two or six of these cell lines. Neither RB1 nor p53 was found to be altered in the fibrosarcoma cell lines tested. An additional transformation marker, autocrine growth-factor production, was observed in all six osteosarcoma cell lines and both fibrosarcoma cell lines examined. Finally, the differentiation state of the osteosarcoma cell lines was investigated via the bone differentiation markers alkaline phosphates and osteocalcin. Alkaline phosphatase activity was observed in four of six osteosarcoma cell lines but not in the two fibrosarcoma cell lines examined. The alkaline phosphatase activity was a result of the expression of the bone/liver/kidney alkaline phosphatase isoform. High-level osteocalcin expression was observed in one of the osteosarcoma cell lines but not in the two fibrosarcoma cell lines examined, although all cell lines demonstrated low-level osteocalcin expression. Together, these data demonstrate that relatively undifferentiated osteosarcomas commonly display c-myc amplification, p53 and RB1 mutation, and autocrine growth-factor production, all of which may play a role in osteosarcomagenesis.
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PMID:Analysis of oncogenes, tumor suppressor genes, autocrine growth-factor production, and differentiation state of human osteosarcoma cell lines. 757 9

A new cell line has been established directly from a spontaneous osteosarcoma on the femur of a 1.5-year-old male mongrel dog and named POS. Doubling time of the cells was approximately 33 hr. Morphologically, spherical cells, fibroblast-like cells, large or small polygonal cells and multinucleated giant cells seemed to be the major component of this cell line. The transmission electron microscopic feature of most of the cells was abundant dilated rough endoplasmic reticulum. Alkaline phosphatase activity as one of the osteoblastic properties was high in this cell line. The tumor tissue produced by the inoculation of the cells into nude mice was histologically identical to the original osteosarcoma.
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PMID:Establishment and characterization of a new cell line from a canine osteosarcoma. 769 11

Establishing regulatory mechanisms that mediate proliferation of osteoblasts while restricting expression of genes associated with mature bone cell phenotypic properties to post-proliferative cells is fundamental to understanding skeletal development. To gain insight into relationships between growth control and the developmental expression of genes during osteoblast differentiation, we have examined expression of three classes of genes during the cell cycle of normal diploid rat calvarial-derived osteoblasts and rat osteosarcoma cells (ROS 17/2.8): cell cycle and growth-related genes (e.g., histone), genes that encode major structural proteins (e.g., actin and vimentin), and genes related to the biosynthesis, organization, and mineralization of the bone extracellular matrix (e.g., alkaline phosphatase, collagen I, osteocalcin, and osteopontin). In normal diploid osteoblasts as well as in osteosarcoma cells we found that histone genes, required for cell progression, are selectively expressed during S phase. All other genes studied were constitutively expressed both at the transcriptional and posttranscriptional levels. Alkaline phosphatase, an integral membrane protein in both osteoblasts and osteosarcoma cells, exhibited only minimal changes in activity during the osteoblast and osteosarcoma cell cycles. Our findings clearly indicate that despite the loss of normal proliferation-differentiation interrelationships in osteosarcoma cells, cell cycle regulation or constitutive expression of growth and phenotypic genes is maintained.
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PMID:Expression of cell growth and bone phenotypic genes during the cell cycle of normal diploid osteoblasts and osteosarcoma cells. 782 87

Alkaline phosphatase solubilized from a human Hodgkin's lymphoma cell line (L428) was compared with purified amphiphilic and hydrophilic forms of the enzyme from human liver, and with the enzyme solubilized from a cultured osteosarcoma cell line (Saos-2). Purified hydrophilic alkaline phosphatases from human placenta and intestine were also compared in some experiments. Alkaline phosphatase was released from the plasma membrane of intact lymphocytes by phosphatidylinositol phospholipase C and thus is anchored to the outside of the plasma membrane by covalently attached phosphatidylinositol. Enzyme released in this way was hydrophilic and that solubilized with Triton X-100 was amphiphilic, as assessed by adsorption to octyl-Sepharose. Lymphocyte alkaline phosphatase, when released from the membrane by phosphatidylinositol phospholipase C or solubilized by Triton X-100, had apparent M(r) values on gradient gel electrophoresis of 227 and 494 kDa, respectively. These values were consistently higher than equivalent ones obtained with enzymes purified from human liver, but were similar to those of cultured osteosarcoma cells. Isoenzyme-specific inhibitors of alkaline phosphatase showed similar patterns of inhibition between the enzyme from L428 cells and the tissue-nonspecific (liver/kidney/bone) isoenzyme from human liver. Heat stabilities were similar for the enzymes from L428 and Saos-2 (bone isoform) cell lines, but differed significantly from those of liver, intestine and placenta. We conclude that the alkaline phosphatase expressed in this lymphoma cell line (L428) has properties that most closely resemble those of the tissue-nonspecific isoenzyme found normally in osteoblasts of bone (bone isoform).
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PMID:Characterization of the alkaline phosphatase expressed on the surface of a Hodgkin's lymphoma cell line. 819 73

The p53 gene undergoes rearrangement in a high percentage of osteosarcomas, resulting in loss of its expression. A p53-null murine osteosarcoma cell line F6 was transfected with either a wild-type or a mutant p53 gene. Stably transfected cell lines were obtained, and their differentiation capabilities were compared in vitro with the parental cell line. Alkaline phosphatase and osteocalcin expression were measured as early and late differentiation markers, respectively. Induction of alkaline phosphatase expression was not affected by the presence of either p53 gene, whereas osteocalcin expression was seen in cells containing the wild-type p53 gene but not in the parental p53-null or mutant-expressing cell lines. That the induction of osteocalcin was intrinsically dependent on the presence of wild-type p53 was also indicated by the use of a temperature-sensitive Val 135 p53 mutant at 32 degrees C; predominant expression of p53 in the wild-type conformation resulted in osteocalcin expression. While the wild-type p53 gene could suppress tumor formation in vivo, the tumors expressing the mutant p53 gene grew two to three times as large as the tumors that did not express p53. Therefore, the absence of end-point differentiation in bone due to p53 rearrangements may contribute to the maintenance of the tumorigenic phenotype in osteosarcomas.
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PMID:Dependence of induction of osteocalcin gene expression on the presence of wild-type p53 in a murine osteosarcoma cell line. 828 Mar 78

We analyzed the endogenous nuclear 1,25-dihydroxy-vitamin D3 (1,25(OH)2D3) receptor (VDR) in rat osteosarcoma (ROS 17/2.8) cells and present biochemical evidence that it is a phosphoprotein. When ROS 17/2.8 cells are labeled metabolically with [35S]methionine, treatment with 10(-8) M 1,25(OH)2D3 elicits a decrease in the electrophoretic mobility of immunoprecipitated VDR in denaturing polyacrylamide gels, a property characteristic of phosphorylated proteins. Similar labeling of cells with [32P]orthophosphate results in a rapid (< or = 30 min), 1,25(OH)2D3-dependent incorporation of 32P into a 54-kDa VDR species that comigrates with the slower migrating receptor species extracted from [35S]methionine-labeled ROS 17/2.8 cells that have been exposed to 1,25(OH)2D3. Alkaline phosphatase treatment of immunoprecipitated VDR from 1,25(OH)2D3-treated cells converts the form of the VDR with reduced mobility to the faster migrating species present in 1,25(OH)2D3-deficient cells. Incubation of ROS 17/2.8 cells with the non-hypercalcemic 1,25(OH)2D3 analog, 22-oxacalcitriol (OCT), produces a level of VDR phosphorylation similar to that elicited by 1,25(OH)2D3 treatment. Transient transfection of osteosarcoma cells with a reporter vector containing a vitamin D responsive element derived from the rat osteocalcin gene yields equivalent transcriptional activation in the presence of either 1,25(OH)2D3 or OCT. Further experiments performed at various 1,25(OH)2D3 concentrations to assess the relationship between receptor phosphorylation and transcriptional activity in intact cells showed a positive correlation between these two parameters, indicating that the 1,25(OH)2D3 hormone stimulates VDR phosphorylation and transcriptional activation in parallel. Finally, highly purified casein kinase II (CK-II) phosphorylates the VDR in a 1,25(OH)2D3-independent, in vitro reaction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The 1,25-dihydroxy-vitamin D3 receptor is phosphorylated in response to 1,25-dihydroxy-vitamin D3 and 22-oxacalcitriol in rat osteoblasts, and by casein kinase II, in vitro. 839 28

Alkaline phosphatase (AP) activity and expression of bone Gla protein (BGP), c-fos, and c-jun were compared in two transplantable osteosarcomas with high potentials for metastasis to the lung. The original spontaneous osteosarcoma (SOS) gradually became histologically undifferentiated, losing its osteogenic activity during serial transfer, whereas the chemical (4-hydroxyaminoquinoline 1-oxide)-induced osteosarcoma (COS) retained osteogenesis. The two osteosarcomas showed similar doubling times and levels of lung metastasis, and strong AP activity was detected on the cell membranes of both. Northern blot analysis revealed that lack of BGP mRNA expression was associated with expression of both c-fos and c-jun proto-oncogenes in SOS. In contrast, neither c-fos nor c-jun mRNAs were detected but BGP mRNA was expressed in the case of COS. These results suggest that the c-fos and c-jun genes may suppress the expression of BGP mRNA relevant to differentiation and osteoid formation in rat osteosarcomas. However, this does not appear to be directly related to proliferative or metastatic biological behavior.
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PMID:Correlation between lack of bone Gla protein mRNA expression in rat transplantable osteosarcomas and expression of both c-fos and c-jun proto-oncogenes. 845 89


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