Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0265264 (HOS)
 1,119 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Soluble chromium (VI) compounds either alone or in combination with 3-methylcholanthrene (MC) were used to transform non-tumorigenic osteoblast-like human osteosarcoma cells (HOS TE85). The Cr(VI) compounds were highly toxic to these cells with LC50 values in the range of approximately 0.5-1.0 microM. Continuous passaging of the treated cells resulted in sustained increase in anchorage-independent (AI) colony formation. Treatment with Cr(VI) and MC resulted in substantial increase in AI growth. At the XVth passage, a number of individual AI colonies were expanded in culture and used for further studies. The cells are refractory in appearance and grow as 'nests' rather than as monolayers. The cell lines have relatively high plating efficiency (PE) in soft agar and respond to promotional effect of phorbol-12-myristate-13-acetate by an increase in PE and in the size and number of AI colonies. While the isolated cells are not tumorigenic when tested in athymic nude mice, most of the lines possess higher levels of plasminogen activator (PA) activity, considered as one of the markers of transformation. This is also reflected in the increase in the steady state level of urokinase type PA mRNA. These results show that Cr(VI) compounds are capable of promoting human cells to an altered phenotype characteristic of a stage in the carcinogenesis cascade.
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PMID:Transformation of non-tumorigenic osteoblast-like human osteosarcoma cells by hexavalent chromates: alteration of morphology, induction of anchorage-independence and proteolytic function. 142 71

The possible carcinogenicity of insoluble chromium (VI) compound, PbCrO4, in human cells has been tested using a nontumorigenic human osteosarcoma cell line (HOS, TE 85). Electron microscopic studies show that PbCrO4 is phagocytosed by HOS cells and accumulates within the vacuoles in the cytoplasm. A number of cell lines have been isolated following multiple treatment of HOS cells with PbCrO4. These cell lines are morphologically different from HOS cells, form anchorage-independent colonies in soft agar and form quickly regressing small tumor nodules in athymic nude mice. The cellular and secreted plasminogen activator (PA) levels of 5 cell lines isolated after PbCrO4 treatment are increased up to 8 fold and up to 10 fold respectively as compared to untreated HOS controls. SDS-PAGE analysis in the presence of copolymerized substrates is consistent with increase in 55 kDa urokinase-type PA (u-PA) and 68 kDa tissue-type PA (t-PA). These results show that PbCrO4 treatment leads to stable phenotypic changes indicative of the transformation of HOS cells.
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PMID:Induction of morphological transformation, anchorage-independent growth and plasminogen activators in non-tumorigenic human osteosarcoma cells by lead chromate. 188 37

We have followed the synthesis and secretion of urokinase-type plasminogen activator (u-PA) and its inhibitor, PAI-1, and matrix metalloproteinases (MMPs) and tissue inhibitor of metalloproteinases (TIMP-1) during differentiation of a human osteoblastic cell line, HOS TE85, and the effect of TNF-alpha on this process. Our results show that the ratio of u-PA/PAI-1 associated with the cell-matrix components increases during differentiation of these cells over a 14-day period. Although TNF-alpha suppresses the induced increase in steady-state mRNA levels of u-PA and PAI-1 during maturation of extracellular matrix (ECM), the u-PA/PAI-1 ratio is altered in such a way that PA activity associated with the ECM is higher than control cells. The expression of MMP-1 is low and remains essentially invariant over a culture period of 14 days. TNF-alpha enhances MMP-1 transcription nearly 12-fold initially, after which mRNA levels drop off but remain significantly higher than the controls. Activities and steady-state mRNA levels of MMP-2 and MMP-9 increase nearly 15-fold during maturation of the ECM, but the level of TIMP-1 mRNA is not appreciably altered. The presence of TNF-alpha suppresses maturation-induced transcription of MMP-2, enhances TIMP-1 transcription, but has little effect on MMP-9 mRNA levels. The data show that chronic exposure to TNF-alpha alters the balance between u-PA/PAI-1 and MMPs/TIMP-1, which favors higher activity of proteinases. Accordingly, the presence of TNF-alpha in chronic inflammatory episodes would be expected to alter bone remodeling by inhibiting maturation of ECM and formation of bone.
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PMID:Differentiation of human osteoblastic cells in culture: modulation of proteases by extracellular matrix and tumor necrosis factor-alpha. 755 48

Inflammatory cytokines like interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) are linked to abnormal cartilage and bone loss in a variety of pathological conditions. We have investigated the effect of TNF-alpha on the synthesis and/or steady-state mRNA levels of collagen, alkaline phosphatase (ALP), plasminogen activators (PAs) and their inhibitor PAI-1, and collagenases (MMPs) and their inhibitor TIMP-1 by human osteoblastic, HOS TE85, cells in monolayer cultures. HOS TE85 cells possess approximately 2000 TNF-alpha receptors per cell with a Kd value of 0.67 nM and receptor of approximately 60 kDa. TNF-alpha enhances urokinase-plasminogen activator (u-PA) activity and steady-state mRNA levels twofold without affecting tissue-plasminogen activator (t-PA) or PAI-1. The increase in u-PA mRNA is due to enhanced transcription of this gene. mRNA levels or activities of collagenase 1 (MMP-1), 72- and 92-kDa gelatinases (MMP-2 and MMP-9) are also nearly doubled with little change in the level of expression of TIMP-1. TNF-alpha does not significantly affect the activity or mRNA levels of ALP. TNF-alpha decreases collagen as well as general protein synthesis. However, the steady-state mRNA for the alpha 2 chain of collagen type I is increased three- to fourfold. These results show that TNF-alpha may increase pathological bone turnover by enhancing the rate of transcription of proteases capable of degrading the nonmineralized osteoid layer and decelerating the maturation of the extracellular matrix formed by osteoblasts.
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PMID:Modulation of proteases and their inhibitors in immortal human osteoblast-like cells by tumor necrosis factor-alpha in vitro. 808 23

Expression of urokinase-type plasminogen activator (u-PA) strongly correlates with a malignant tumor cell phenotype. In the multistep process of metastasis, different cellular functions are influenced by urokinase. The enzyme is known to be effective via both proteolytical and signal transduction mechanisms. In the present study, the osteosarcoma cell line MNNG/HOS was transfected with a vector capable of expressing an antisense transcript, complementary to 1,021 bases of the 3' end of u-PA cDNA. This construct was most effective in reducing u-PA expression in previous experiments. Stably transfected antisense (as) cell lines were characterized and compared with the parental MNNG/HOS. Antisense transfection of MNNG/HOS gave the following results: (1) stable incorporation of the construct into the genome of as-clones, as detected by Southern blot analysis; (2) decreased mRNA level of u-PA, as detected by Northern blot analysis; (3) approximately 50% reduced enzyme expression in cell culture medium and cell homogenate; and (4) unchanged cellular proliferation activity and u-PAR expression. In further functional analysis, as-clones showed (1) significantly reduced invasion and motility in modified Transwell chambers (random migration and chemotaxis with collagen I as a chemoattractant); (2) significantly reduced adhesion on matrices of collagen I and vitronectin; (3) unchanged adhesion properties on Matrigel matrix; and (4) reduced metastatic potential to lungs and especially liver in chick embryos after i.v. infection into chorioallantoic membrane veins. Our data show that in MNNG/HOS urokinase influences cellular malignancy by promoting migration and selective adhesion. These specific functions were notable in addition to the effects on invasion and basement membrane degradation.
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PMID:Antisense inhibition of urokinase: effect on malignancy in a human osteosarcoma cell line. 963 7

In the multistep process of tumor metastasis, different cellular functions are known to be influenced by the urokinase plasminogen activator (u-PA). In different types of malignancies, u-PA has been shown to correlate strongly with a malignant tumor cell phenotype. Besides its proteolytic activity, the enzyme is effective by signal transduction mechanisms. To elucidate u-PA functions in osteosarcoma, in the present study, the osteosarcoma cell line MNNG/HOS was transfected with an antisense (as) expression vector encoding the 3' end of u-PA-cDNA. Several stably transfected cell clones were characterized and compared with the parental cell line. The antisense transfection resulted in: (1) stable incorporation of the vector construct into cellular genome, as demonstrated in Southern blot; (2) decreased u-PA expression in Northern blot; (3) 50% reduced u-PA protein expression in both cell homogenate and cell culture medium; (4) unchanged cellular proliferation and u-PAR (urokinase plasminogen activator receptor) expression. In comparing functional analysis, as-clones showed (I) significant reduced in vitro invasion and motility (chemotaxis with collagen I); (II) significantly reduced adhesion activity to both vitronectin and collagen I matrices but unchanged adhesion on matrigel; (III) reduced in vivo metastasis in chick embryos after i.v.-application. All together, this data show that malignancy of the osteosarcoma cell line MNNG/HOS is positively influenced by urokinase in terms of migration and selective adhesion. Both effects were observed besides the previously described enzyme functions in tumor cell invasion and basement membrane degradation.
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PMID:[Antisense inhibition of urokinase in a human osteosarcoma cell line]. 1009 29

Increased activity, membrane association, and secretion of cathepsin B have been shown to correlate positively with invasiveness and the metastatic properties of many tumor entities. Cathepsin B is able to directly facilitate invasion by degrading extracellular matrix components or to indirectly facilitate invasion by activating other matrix-degrading proteases like the urokinase-type plasminogen activator. To investigate the role of cathepsin B in bone tumor invasion, the osteosarcoma cell line MNNG/HOS was stably transfected with an expression vector capable of expressing the antisense cDNA transcript of cathepsin B. Five stably transfected antisense cell clones, the control (vector) cell clones, and the parental cells were characterized. At first, the stable incorporation of the constructs was demonstrated by Southern blot analysis. In ELISA assays, all antisense clones showed a significant reduction at the cathepsin B antigen level (about 70%) as compared with the control cell clones and MNNG/HOS. Similar results were obtained for cathepsin B activity in the antisense-transfected cells. In the antisense cell clones, Northern blot analysis and reverse transcription-PCR revealed a considerable decrease of approximately 50% in the levels of cathepsin B mRNA. Expression of cathepsins L and K (sequence homologies) was not affected. The invasive potential and migration of untransfected and transfected tumor cell clones in vitro were analyzed in Transwell chambers. Antisense-transfected cells showed a markedly lower invasion and motility than did MNNG/HOS and the controls. Adhesion to collagen I and matrigel matrices was not affected. These results demonstrate that cathepsin B is involved in the complex proteolytic processes in invasive osteosarcomas.
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PMID:Inhibitory effects of antisense cathepsin B cDNA transfection on invasion and motility in a human osteosarcoma cell line. 1060 50