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)

Previous studies have shown that bone marrow, especially the bone microenvironment, may play an important role in the pathogenesis of multiple myeloma (MM). To elucidate the relationship between myeloma cells and bone cells, mainly osteoblasts, we have established a coculture system between two interleukin-6 (IL-6)-dependent myeloma cell lines, XG1 and XG6, and the osteosarcoma cell lines Saos-2 and MG63. Both osteosarcoma cell lines have retained major functions of normal osteoblasts; principally, the capacity to produce hematopoietic growth factors (including IL-6) and osteocalcin, a noncollagenic protein essential in the bone formation process. Because IL-6 is a critical growth factor in MM, we have examined the IL-6 osteoblastic cell production in our coculture system. XG1 cells strongly upregulate IL-6 production by MG63 and Saos-2 cells. Of major interest, the triggering of IL-6 is totally dependent on the physical contact between myeloma cells and osteoblastic cells, contact that is partly mediated by CD44, CD56, and fibronectin interactions. Osteocalcin production by MG63 and Saos-2 cells has previously been shown to be dependent on 1,25-(OH)2D3. We demonstrate that XG1 and XG6 cells reduced the amount of osteocalcin in MG63 coculture cell supernatants, a reduction that is partly mediated by a soluble factor and by cell-to-cell contact. Notably, whereas one of the myeloma cell lines, XG6, has lost its capacity to stimulate IL-6 production by osteoblastic cell lines, both XG1 and XG6 cell lines remain able to reduce the osteocalcin amount, indicating that IL-6 and osteocalcin levels are regulated by two different pathways. In conclusion, these data strongly support the concept that the bone microenvironment is directly modified by contact with myeloma cells and are consistent with the characteristics observed in vivo in patients with MM patients, ie, abnormally high IL-6 and low osteocalcin levels, respectively.
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PMID:Myeloma cells upregulate interleukin-6 secretion in osteoblastic cells through cell-to-cell contact but downregulate osteocalcin. 757 10

Knowledge of the expression pattern of the cell surface glycoprotein CD44 in the development and differentiation of bone is limited. We investigated CD44 expression (a) in bone sections of 21-day-old fetal rat calvaria (RC), metatarsals, and tibiae, (b) in primary cultures of RC cells undergoing differentiation in vitro, and (c) in three rat osteosarcoma cell lines: ROS 17/2.8, UMR 106.01, and UMR 106.06. By immunocytochemistry, Western, Northern and reverse transcription polymerase chain reaction analyses, we found that osteoblastic cells express the 'hematopoietic' or 'standard' CD44 (CD44s) isoform. Osteoblastic cells in vivo and in vitro stained at all detectable stages of differentiation, but intercellular heterogeneity of CD44s staining was evident, with lesser staining in preosteoblastic cells and greater staining in mature osteoblasts and osteocytes. As cells in RC cultures differentiated and formed bone in vitro, CD44s mRNA and protein levels as measured on immunoblots were invariant. All three osteosarcoma cell lines expressed CD44s mRNA and protein. The synthetic glucocorticoid dexamethasone, which stimulates osteogenesis in RC cells in vitro and regulates a number of osteoblast-associated genes, had no apparent effect on either CD44s protein or mRNA levels. The widespread presence of CD44s in osteoblastic cells at various maturational stages suggests that further analyses will be required to determine what role CD44s may play in osteogenesis and in bone tissue organization.
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PMID:CD44 expression in fetal rat bone: in vivo and in vitro analysis. 860 25

The standard form of CD44 (CD44H) is a transmembranous glycoprotein, widely distributed on a variety of human lymphoid cells, epithelial cells and tumours. CD44 has many variant forms, which are generated by alternative splicing. In recent years, CD44 has been reported to be related to the degree of tumour differentiation, tumour cell invasion, and metastasis. We investigated 44 tumour specimens in 39 patients with osteosarcoma immunochemically to analyse the expression of CD44 standard (CD44H) and variant exon-encoded gene products (CD44v3, v4, v5, v6, v7, v9, and v10). Furthermore, the relationship between CD44 expression and the clinical outcome of patients with osteosarcoma was analysed. Membrane accentuation and exclusive cytoplasmic reactivity were analysed as separate staining patterns. Tumour cells and some multinucleated giant cells were markedly stained. CD44H, v3, v4, v5, v6, v7, v9, and v10 were expressed in 85%, 49%, 54%, 59%, 46%, 5%, 28%, and 10% of the specimens respectively. The cumulative 5-year metastasis-free survival was 58% in CD44v6-negative cases and 24% in CD44v6-positive cases (P=0.046). However, the cumulative 5-year metastasis-free survival was not significantly different between cases positive and negative for other variants of CD44. Multivariate analysis (Cox proportional-hazard model) with CD44v6 expression (positive or negative), chemotherapy (intensive or non-intensive), tumour site (proximal or distal), and age (at least 30 years or less than 30 years) showed that expression of CD44v6 and chemotherapy were important prognostic factors in patients with osteosarcoma. Overexpression of CD44 isoforms containing variant v6 is correlated with poor prognosis in patients with osteosarcoma.
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PMID:Expression of CD44 variants in osteosarcoma. 1054 73

The effect of CD44-phenotypic expression on metastasis to the lung was studied using a spontaneous murine osteosarcoma-derived cell line, POS-1, stimulated with lipopolysaccharide (LPS). POS-1 cells were inoculated into the hind paws of 20 C3H/HeJ mice and produced a visible mass in all mice in 5 weeks, and these transplanted tumors resulted in lung metastasis in all mice. The number of metastatic foci in the lungs was 12.0+/-2.1 (mean+/-SD) with LPS-stimulated cells, which was significantly higher than that of unstimulated cells (5.8+/-1.4; N=10 for each; P<0.05). Hyaluronate (HA), a ligand of CD44, inhibited a number of lung metastases in a dose-dependent manner (0.5% HA, 3.0+/-1.1; 0.005% HA, 5.1+/-1.5; without HA, 8.6+/-1.7; N=10 for each; P<0.05, each group with HA versus the group without HA). Adhesion assay by coculturing POS-1 cells and lung microvascular endothelial cells on culture plate showed that the adhesion was significantly lower in HA treated POS-1 than those without HA (1.18+/-0.12 and 2.74+/-0.17, respectively, P<0.05). These results suggest that lung metastasis was accelerated by up-regulation of CD44.
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PMID:Acceleration of lung metastasis by up-regulation of CD44 expression in osteosarcoma-derived cell transplanted mice. 1146 96

CD44 is a family of cell surface glycoproteins that not only function as receptors to hyaluronan and other extracellular matrix ligands but also is implicated in the invasiveness and metastasis of malignancies. The expression of CD44 and its variant isoforms was evaluated by immunohistochemistry in primary osteosarcoma, and the metastatic significance and prognostic relevance were assessed. Fifty formalin-fixed, paraffin-embedded conventional osteosarcoma samples were immunostained with monoclonal antibodies to CD44s, CD44v5, and CD44v6. When more than 50% of the tumor cells were stained, the result was regarded as ++ (overexpression). Staining patterns of CD44 mainly were membranous with a minor cytoplasmic pattern contribution. CD44s was overexpressed in 16% (eight of 50), CD44v6 in 20% (10 of 50), and CD44v5 in 46% (23 of 50) of the osteosarcomas. Of 26 patients with metastasis, CD44s was overexpressed in six (23%), CD44v6 in four (15%), and CD44v5 in 17 (65%). Overexpression of CD44v5 correlated significantly with metastasis. The survival rate of the patients in the CD44v5-positive (overexpressed) group was significantly lower than that of the patients in the CD44v5-negative group. Overexpression of CD44v5 may play a role in the metastatic behavior of osteosarcoma and may be a prognostic parameter of osteosarcoma.
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PMID:Expression of CD44 isoforms correlates with the metastatic potential of osteosarcoma. 1185 42

The possibility that a sinusoidal 50 Hz magnetic field with a magnetic flux density of 0.5 mT can induce variations in the expression of cell adhesion molecules (CAMs) in two human osteosarcoma cell lines (MG-63 and Saos-2) was investigated. In particular, the expression of two important integrins, VLA-2, the receptor for collagen, and VLA-5, the receptor for fibronectin, as well as CD44, were examined in both cell lines after these had been exposed for 7 and 14 days to a 50 Hz, 0.5 mT field. Cell surface morphology (scanning electron microscopy), cell growth characteristics (growth curves and cell cycle phase distribution), and cell death (necrosis and apoptosis) were also examined. The results demonstrate that no variations in surface morphology and cell death occurred between control and exposed cells in both MG-63 and Saos-2 cells, while significant changes were noted in cell growth and fibronectin and CD44 expression in MG-63 cells. The results are discussed in view of the important role that CAMs play in controlling various cancer cell functions, particularly proliferation and metastasis.
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PMID:Effects of a 50 Hz sinusoidal magnetic field on cell adhesion molecule expression in two human osteosarcoma cell lines (MG-63 and Saos-2). 1282 Feb 90

This study demonstrates that in human osteosarcoma cells treatment with 3-aminobenzamide (3-AB), a potent inhibitor of poly(ADP-ribose) polymerase (PARP), induces morphological and biochemical features of differentiation, the duration of which depends on whether or not the normal RB gene is expressed. In Saos-2 cells expressing a non-functional Rb protein, 3-AB treatment induced the formation of transient, short dendritic-like protrusions. In RB-transfected-Saos-2 cells (a clone previously generated in our laboratory that shows stable expression of wild-type Rb protein), 3-AB induced marked and prolonged changes with the formation of long dendritic-like protrusions and the appearance of stellate (osteocyte-like) cells. In MG-63 cells producing a wild-type Rb protein, 3-AB treatment had more marked effects, with a larger number of cells assuming the stellate appearance of osteocytes, which were connected to each other via junctions resembling small channels. Regardless of cell type, at some point after 3-AB treatment the differentiative attempt failed and the cells died. Death was apoptotic, as demonstrated by chromatin condensation and fragmentation, specific cleavage of PARP and Lamin-B, processing of caspase-3 and the appearance of Bax immunoreactive species. Enzymatic assay and RT-PCR of alkaline phosphatase (ALP) - an enzyme whose levels markedly decrease when osteoblasts undergo terminal differentiation into osteocytes - showed that 3-AB treatment markedly lowered ALP expression. Simultaneously, 3-AB treatment markedly increased the expression of CD44, a transmembrane multifunctional adhesion molecule and sensitive marker of osteocytic differentiation. This study hypothesizes a cross-talk between pRb and PARP and suggests that PARP may be a useful target for anticancer drugs.
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PMID:The effect of 3-aminobenzamide, inhibitor of poly(ADP-ribose) polymerase, on human osteosarcoma cells. 1461 22

Adiponectin has until now been considered to be synthesized and secreted exclusively by the adipose tissue, and is reported to influence energy homeostasis and insulin sensitivity. It is also known that body weight is positively correlated with increased bone mineral density and decreased fracture risk. The mechanisms explaining this relation, however, are not completely understood. We report a link between adiponectin and bone homeostasis by demonstrating transcription, translation, and secretion of adiponectin, as well as expression of its receptors, AdipoR1 and AdipoR2, in bone-forming cells. We show that adiponectin and the receptors are expressed in primary human osteoblasts from femur and tibia. The phenotype of bone cells was confirmed by the high expression levels of alkaline phosphatase, collagen type 1, osteocalcin, and CD44, and the formation of mineralization nodules. Immunostaining with monoclonal antibodies also demonstrated the presence of adiponectin in human osteosarcoma cells and normal osteoblasts. Both mRNA expression and secretion of adiponectin to the medium increased during differentiation of human osteoblasts in culture. The adiponectin mRNA level increases in osteoblasts cultured 3 and 7 days in the presence of dietary fatty acids and supplementation of culture medium with recombinant adiponectin enhances the proliferation of murine osteoblasts. The regulation and detailed function of adiponectin in bone still remains obscure, but our findings suggest a functional role in bone homeostasis. If so, adiponectin may provide an important signal linking fat and body weight to bone density.
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PMID:Adiponectin and its receptors are expressed in bone-forming cells. 1545 91

Several studies have suggested that increased production of hyaluronan (HA) is associated with metastatic behavior in various malignant tumors. To our knowledge, HA molecular weights required for metastasis are still unsolved in osteosarcoma. We examined the size of HA and hyaluronan synthase (HAS) isoforms related to biological functions required for metastasis in the LM8 stably highly metastatic osteosarcoma cell line. We found that HA of molecular weight which HAS3 produces enhanced biological functions related to metastasis such as cell proliferation, invasion, and degradation of extracellular matrix. Moreover, cell proliferation and invasion were inhibited by suppressing the activity of HAS3 expressed in LM8 cells, using hyaluronan synthase suppressor, 4-methylumbelliferone (MU). HA with the molecular weight related to HAS2 was the most adherent to CD44 in LM8 cells, suggesting that HAS2 may play an important role in pericellular coat formation. These results suggest that HAS3-related HA enhances crucial biological activities necessary for metastasis and that HAS2-related HA offers an advantageous environment for osteosarcoma cells.
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PMID:HAS3-related hyaluronan enhances biological activities necessary for metastasis of osteosarcoma cells. 1677 98

The effects of chemically induced hypoxia and ionizing radiation on the adhesive properties of MG-63 human osteosarcoma three-dimensional spheroids were investigated. Hypoxia was induced by addition of CoCl2 to small, nonhypoxic spheroids and verified by HIF-1alpha expression. In addition, the possible role of important cell adhesion molecules involved in tumor dissemination in inducing adhesive changes were also studied. In particular, two key integrins (i.e., the alpha chain of the fibronectin receptor, alpha5, and the alpha chain of the collagen receptor, alpha2), an important member of the immunoglobulin superfamily (CD54 or ICAM-1) and the strategic molecule CD44 (H-CAM, the principal receptor for hyaluronan) were examined. Because of the important role of fibronectin in adhesive processes, variations in this extracellular matrix component were also examined. The results seem to indicate that CoCl2-induced hypoxia greatly increases adhesion of MG-63 spheroids to both tissue culture plates and plates coated with fibronectin or collagen when compared to controls, while ionizing radiation induces a great decrease in this attachment. Furthermore, chemically induced hypoxia also partially inhibits the effects of ionizing radiation. The data also show that these adhesive changes are accompanied by concomitant variations in the expression of alpha5 and alpha2 integrins, CD44, and CD54 and fibronectin.
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PMID:Hypoxia and ionizing radiation: changes in adhesive properties and cell adhesion molecule expression in MG-63 three-dimensional tumor spheroids. 1679 17


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