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

Osteosarcomas contain variable amounts of bony tissue, but the mechanism of bone formation by osteosarcoma is not well understood. While a number of cultured human osteosarcoma cell lines have been established, they are maintained by different media and differ qualitatively with regard to bone formation. We examined different media for their ability to support bone formation in vitro and found the alpha-modification of Eagle's minimal essential medium supplemented with beta glycerophosphate was best for this purpose, because it contained the proper calcium and phosphate concentrations. Subsequently, we compared seven human osteosarcoma cell lines under the same experimental conditions to clarify their ability to induce bone formation. NOS-1 cells most frequently exhibited features of bone formation in vitro and in nude mice. Collagen synthesis by tumour cells themselves seemed to be the most important factor for bone volume. However, even HuO9 cells, which lacked collagen synthesis and failed to form bone in vitro, successfully formed tumours containing bone in nude mice. Histological analysis of HuO9 cells in diffusion chambers implanted in nude mice and the findings of polymerase chain reaction indicated that the phenomenon was probably due to bone morphogenetic protein.
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PMID:Bone formation in vitro and in nude mice by human osteosarcoma cells. 775 79

Interleukin 6 (IL-6) exerts well-established effects on cells of the immune system as well as on various other cell types. We have investigated the effects of IL-6 produced by human osteosarcoma cells on tumor cells from two clonal human osteosarcoma cell lines, KSU.C3 and NOS-1.C8. We were unable to identify any effects of IL-6 such as cell proliferation, alkaline phosphatase activity, osteocalcin production, or collagen synthesis on the bone-forming phenotypes. However, the KSU.C3 cell line, which showed a little osteoid and no bone formation and was accompanied by a few osteoclasts in the xenografted tumors, produced high levels of IL-6, the production of which was quickly and easily stimulated by various agents. On the other hand, the NOS-1.C8 cell line, which formed abundant osteoid or bone and was accompanied by no osteoclasts in the xenografted tumors, produced no detectable levels of IL-6 without stimulation, and the production of IL-6 in response to IL-1 beta was slower. Our data suggest that IL-6 produced by osteosarcoma cells does not play an important role in bone formation, but may mediate osteoclastic bone resorption.
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PMID:Differential production of interleukin 6 in human osteosarcoma cells and the possible effects on neoplastic bone metabolism. 810 98

Osteosarcomas are malignant tumours producing osteoid and/or bone. It is difficult to distinguish tumour bone formation from reactive, based on their morphological features alone. The objective of this study was two-fold: to clarify the origins of bone-forming cells in human osteosarcoma transplanted into nude mice; and to examine the role of bone morphogenetic proteins (BMPs) in the tumour-induced osteogenesis. DNA in situ hybridization was carried out with digoxigenin (DIG) polymerase chain reaction (PCR) labelled DNA probes for human-specific 'Alu' and mouse-specific 'mouse L1 (m-L1)' genes. Human osteosarcoma cells, established cell lines of NOS-1, NOS-2, and HuO9, were transplanted separately into nude mice. Bone-forming cells of the bone in the NOS-1 or NOS-2 tumours were positive for Alu, while they were negative for m-L1. The cells lining the surface of trabeculae in the HuO9 tumour were positive for Alu, but a few of them were also positive for m-L1. The m-L1-positive cells expressed mouse osteocalcin and type 1 collagen mRNAs. These facts suggest that the mouse cells were involved in osteoid synthesis of the HuO9 tumour. The NOS-1 or NOS-2 tumours expressed human BMP 2-7 mRNAs, whereas the HuO9 tumour expressed human BMPs 2, 4, 5, and 7. The osteogenetic potential of the tumours may depend on the expression patterns of BMPs. These results demonstrate two distinct types of bone formation, by tumour cells and by an admixture of tumour and non-tumour cells. The present study showed that the HuO9 tumour produces chimeric bone formation. This is the first report to demonstrate the relationships between tumour cells and non-tumour cells in bone formation, using genetic markers.
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PMID:Origin of bone-forming cells in human osteosarcomas transplanted into nude mice--which cells produce bone, human or mouse? 971 49

To demonstrate three-dimensionally the process of the collagen fibril growth, the bottom of culture dishes with human osteosarcoma cells (NOS-1) and their extracts were examined by conventional scanning electron microscopy (SEM). Backscattered electron (BSE) imaging of SEM was also applied to the specimens, which were stained with phosphotungustic acid and uranyl acetate. Conventional SEM images showed several stages of collagen fibril assembly. Short collagen fibrils with tapered ends were distributed at the bottom of the dish just beneath and/or around the cultured cells; they were 1 microm long and 20-30 nm in diameter at the thickest middle portion. These fibrils were often twisted and united in a right helical direction, and consequently increased in length (5-10 microm) and diameter (more than 100 nm). In BSE images, the periodical bands stained with phosphotungstic acid and uranyl acetate were visualized throughout the individual fibrils. The banding pattern indicated that the polarity of the collagen molecules was unidirectional; namely, that all molecules were pointed in the same direction throughout the length of the fibrils.
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PMID:Growth of collagen fibrils produced by human osteosarcoma cells: high-resolution scanning electron microscopy. 1059 43

The effects of recombinant human bone morphogenetic protein-2 (rhBMP-2) on cell growth were studied in three human osteosarcoma cell lines, NOS-1, HuO9, and HuO-3N1; one human prostate cancer cell line, PC-3; and one human breast cancer cell line, OCUB-1M. The growth of these cell lines was not promoted by rhBMP-2 at concentrations of 50, 100, 250, and 500 ng/ml, as evaluated by colorimetric 3 (4,5-dimethyl-thiazol-2-yl)-2,5 diphenyl tetrazolium bromide (MTT) assay. Furthermore, the protein induced osteogenic differentiation, characterized by increased alkaline phosphatase activity, and increased production of type I collagen and gamma-carboxylated osteocalcin in NOS-1 cells. The results of this study may suggest the feasibility of using rhBMP-2 for the reconstruction of bone defects caused by malignant tumors, although the data are still preliminary and require further investigation.
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PMID:Effects of bone morphogenetic protein-2 on human tumor cell growth and differentiation: a preliminary report. 1118 Sep 25

Osteosarcoma is a malignant tumor with poor prognosis, and lack of accurate prognostic factors is one of the reasons that make this tumor difficult to cure. The heparin-binding growth factor, midkine is involved in generation and progression of many types of tumors. However, the relationship between midkine and osteosarcoma has been unclear. We show here that midkine is overexpressed in osteosarcoma and the level of midkine expression is correlated with prognosis (P<0.05; log-rank test). Treatment with functional antibodies against midkine suppresses growth of osteosarcoma cell lines, 9N2, 3N1, Saos-2, and NOS-1, to 25-65% of untreated controls. Our results suggest that midkine is useful as a prognostic marker, and is a candidate therapeutic target for osetosarcomas.
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PMID:Midkine as a novel target for antibody therapy in osteosarcoma. 1750 84

Polycomb group proteins control the transcriptional memory of cells by maintaining the stable silencing of specific sets of genes through chromatin modifications. Polycomb group protein complexes control gene repression through recruitment of histone deacetylase. This recruitment leads to trimethylation of Lys27 of histone H3 (H3K27). Histone H3K27 trimethylation is a property of stably silenced heterochromatin. EZH2 and BMI-1 are pivotal components of polycomb group protein complexes. Increased EZH2 levels have been found in several malignancies and reported as a molecular biomarker of poor prognosis. Similarly, BMI-1 has also been found to be associated with malignant transformation. In addition, inhibition of EZH2 or BMI-1 inhibits the growth of various types of malignancies. The expression of BMI-1 and EZH2 in human osteosarcoma has not been clearly determined. We examined the potential involvement of aberrant polycomb group protein expression in the pathogenesis of osteosarcoma. Real-time PCR revealed that expression of EZH2 in 143B, HOS, NOS-1 and Saos2 was increased compared to normal osteoblasts. BMI-1 was also up-regulated in 143B, HOS and NOS-1. Expression of EZH2 and BMI-1 were up-regulated in osteosarcoma patient biopsy specimens compared to normal bone. Immunohistochemical examinations showed that EZH2 and BMI-1 were up-regulated in osteosarcoma cells and that trimethylation of histone H3K27 was increased. We examined the effects of knock down of EZH2 and BMI-1 by shRNA. Unexpectedly, the knock-down of EZH2 and BMI-1 did not prevent osteosarcoma growth either in vitro or in vivo. Our findings suggest that EZH2 and BMI-1 may be tumor-associated antigens of osteosarcoma, but are not useful molecular targets of osteosarcoma treatment.
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PMID:The knock-down of overexpressed EZH2 and BMI-1 does not prevent osteosarcoma growth. 2012 6

The present study examined the three-dimensional process of collagen fibril formation in the human osteosarcoma cell line NOS-1 by conventional scanning electron microscopy (SEM) and atomic force microscopy (AFM). SEM images showed collagen fibril formation on the bottom of culture dishes after 1 week of culture. The collagen fibrils had diameters of 30-100 nm. The surfaces of individual fibrils had characteristic grooves and ridges with periodicities of 60-70 nm. AFM images showed that the newly formed collagen fibrils were 30-300 nm in diameter and possessed characteristic grooves and ridges with periodicities of 60-70 nm. The thicker collagen fibrils contained thinner (approximately 30 nm thick) subfibrils that ran in a helical direction along the long axis of the thicker fibrils. Furthermore, twisted structures of collagen fibrils, which possessed a characteristic rope-like structure, were also identified. The ultrastructure of the collagen fibrils was clearly imaged in liquid medium by AFM, and the process of collagen fibril assembly was successfully analyzed under conditions much closer to the physiological state than those afforded by transmission electron microscopy or SEM. AFM also provided a precise morphological measurement, particularly of the vertical distance, of collagen fibrils with nanometer-scale resolution in liquid conditions.
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PMID:Observation of collagen fibrils produced by osteosarcoma cells using atomic force microscopy. 2419 68