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

Under substrate adherent conditions, integrin gene expression can be regulated by transforming growth factor-beta, interleukin-1 beta, and prostaglandins. This report demonstrates a new mechanism that can differentially control the expression of several integrins. When MG-63 osteosarcoma cells are maintained in suspension, up-regulation of several integrin alpha-subunits takes place. Within as little as 4 h, the mRNA levels for both the alpha 2- and alpha 4-subunits are increased 4- and 6-fold, respectively. It was found that mRNA levels for the alpha 2-, alpha 4-, and alpha v-subunits were markedly increased in several differentiated cell lines under nonadherent conditions; however, cells that did not express a given integrin under substrate adherent conditions also did not express this integrin when maintained in suspension. The alpha 5-subunit did not upregulate during suspension growth. By immunocytochemistry, changes in integrin mRNA levels were confirmed at the protein level. Both cytochalasin B and a phorbol ester were found to induce the expression of the alpha 2-subunit, but not the alpha 4- and alpha 5-subunits, in a dose-dependent fashion. Many investigators have documented changes in gene expression that result from changes in "cell shape." These phenomena may result from up-regulation of integrin gene expression induced by the lack of substrate adherence.
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PMID:Regulation of integrin gene expression by substrate adherence. 142 94

We report the identification of cell surface glycoproteins that bind transforming growth factor-beta (TGF-beta) in an isoform-specific manner, and are distinct from TGF-beta receptors I and II or the TGF-beta binding proteoglycan beta-glycan. The novel TGF-beta binding proteins have been identified in various cell lines including fetal bovine heart endothelial cells and MG-63 human osteosarcoma cells. They include proteins of 90-100 and 180 kDa that preferentially bind TGF-beta 1 (KD 0.1-0.2 nM) and proteins of 60 and 140 kDa that preferentially bind TGF-beta 2 (KD 0.5-1 nM). The 180-kDa TGF-beta 1 binding protein and the 60- and 140-kDa TGF-beta 2 binding proteins can be released from the cell surface by treatment with phosphatidylinositol-specific phospholipase C, suggesting that these proteins are attached to the plasma membrane through a phosphatidylinositol anchor. The expression of these three proteins as well as their sensitivity to phosphatidylinositol-specific phospholipase C is cell line-dependent. The 90-100-kDa TGF-beta 1 binding proteins are components of a 190-kDa disulfide-linked complex. The structural properties of these proteins and their high affinity and selectivity for different TGF-beta isoforms defines them as a novel class of cell surface TGF-beta binding proteins.
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PMID:Isoform-specific transforming growth factor-beta binding proteins with membrane attachments sensitive to phosphatidylinositol-specific phospholipase C. 165 36

Secreted phosphoprotein I (SPPI; osteopontin), a highly phosphorylated form of which has been associated with cell transformation, is one of the major phosphorylated proteins in bone. Populations of rat bone cells derived from fetal calvariae, neonatal parietal bone and a rat osteosarcoma cell line (ROS 17/2.8) produce several forms of the protein, the major forms having apparent molecular masses of 55 and 44 kDa by SDS/PAGE on 15% (w/v) cross-linked gels and of 60 and 56 kDa on 10% gels. Northern blot analysis of SPPI mRNA using total cellular RNA revealed a single 1.5 kb mRNA species, indicating that the nascent protein chains of these phosphoproteins are identical. On treatment of the cells with transforming growth factor-beta (TGF-beta; 1 ng/ml), the levels of SPPI mRNA and the synthesis of the 55 kDa phosphoprotein, but not of the 44 kDa phosphoprotein, were increased by 1.8-4.5-fold in the normal osteoblastic cells, the stimulation first being evident at 3 h and reaching a maximum at 12 h. In the transformed ROS 17/2.8 cells, TGF-beta did not alter significantly the SPPI mRNA level or the synthesis of either the 55 kDa or the 44 kDa SPPI over the 24 h period studied. By comparison, neither the steady-state levels of SPARC (secreted protein, acidic, rich in cysteine) mRNA nor the synthesis of SPARC protein were affected significantly by the addition of TGF-beta to any of the osteoblastic bone cells. The half-lives for SPPI and SPARC mRNAs in the osteoblastic calvarial cells were calculated to be 18 h and greater than 50 h respectively, in both the presence and the absence of TGF-beta. Since the stability of the mRNA was unchanged by TGF-beta and the increased expression of SPPI mRNA could be blocked by cycloheximide, TGF-beta appears to increase transcription of the SppI gene indirectly by stimulating the synthesis of a protein that promotes transcription. These results demonstrate that several forms of SPPI are synthesized constitutively by bone cells, and that there are clear differences in the regulation of SppI gene expression by TGF-beta in normal bone cells compared with the tumorigenic ROS 17/2.8 cells. The differential responses of normal osteoblastic cells to TGF-beta in the expression of SPPI and the selective stimulation of specific forms of the SPPI protein may be important in bone repair and remodelling.
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PMID:Regulation of transformation-sensitive secreted phosphoprotein (SPPI/osteopontin) expression by transforming growth factor-beta. Comparisons with expression of SPARC (secreted acidic cysteine-rich protein). 199 53

Clinical observations have demonstrated a positive effect of estrogens and androgens on the maintenance of structural bone integrity. This study examines the direct effects of androgenic hormones on the osteoblast-like human osteosarcoma cell line, HOS TE85. Employing radiolabeled dihydrotestosterone (DHT), 2800 saturable, high-affinity (dissociation constant = 0.66 nM) androgen binding sites were detected per HOS TE85 cell. Androgen binding was specific in that DHT and testosterone (T) displayed significantly greater competition than the progestins, progesterone and medroxyprogesterone. The expression of androgen receptors in HOS TE85 cells was further substantiated by Northern analysis. A human androgen receptor complementary DNA probe revealed a 9.5 kilobase transcript which corresponds to the predominant human androgen receptor transcript detected in human male reproductive tissues. Androgens were also found to elicit biological responses in HOS TE85 cells. Physiological concentrations of DHT and T decreased HOS TE85 cell proliferation as assessed by cell count. This finding suggests that DHT may also play a role in osteoblast differentiation. In support of this hypothesis, treatment with T (24 h, 10 nM) enhanced the abundance of both alpha 1(I)-procollagen messenger RNA (mRNA) (5-fold) and transforming growth factor-beta mRNA (2.2 fold). The nonaromatizable androgen DHT (24 h, 10 nM) elicited an increase in the steady state concentration of alpha 1(I)-procollagen mRNA similar to the increase observed with T treatment. Thus, in addition to the recent discovery of estradiol receptors and estrogenic regulation of HOS TE85 cells, it is now evident that these osteoblast-like osteosarcoma cells also express high affinity androgen binding sites and can respond biologically to androgens.
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PMID:High-affinity androgen binding and androgenic regulation of alpha 1(I)-procollagen and transforming growth factor-beta steady state messenger ribonucleic acid levels in human osteoblast-like osteosarcoma cells. 203 57

Among several bioactive substances known as coupling factors, transforming growth factor-beta (TGF-beta), interleukin-1 (IL-1), and prostaglandin (PG) E1 and E2 increased not only the activity of alkaline phosphatase but also the rate of incorporation of 45Ca2+ into ROS 17/2.8 during a 3-day culture: the former two factors are known to be formed at the site where bone is resorbed, while PG's are known as one of the factors involved in bone resorption. Parathyroid hormone, another hormone that affects bone metabolism, elevated the incorporation of 45Ca2+ by and decreased the alkaline phosphatase activity of the cells. The facts indicate the possibility that the osteoblastic cells are involved in the transport of calcium ions when bones are being resorbed. On the other hand, when these osteosarcoma cells were cultured in DMEM containing ascorbate and beta-glycerophosphate, followed by staining with silver nitrate by the procedure of von Kossa, there appeared many groups of cells that were positively stained as dark brown spots. Cells were then cultured under the same conditions in the presence of radioactive calcium, and the radioactivity accumulated was measured. The result showed that the presence of both ascorbate and beta-glycerophosphate in the culture medium dramatically increased the accumulation of 45Ca2+. It appears from these facts that ROS 17/2.8 cells are capable of incorporating and/or accumulating calcium ion if they are cultured under appropriate conditions. These cells will probably be able to produce a calcified matrix in vitro.
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PMID:[Effects of L-ascorbic acid and bone metabolism factors on alkaline phosphatase activity of and 45Ca2+ incorporation by ROS 17/2.8 cells]. 213 81

The influence of transforming growth factor-beta (TGF-beta) on the expression of different forms of small proteoglycans was investigated in human skin fibroblasts and in a human osteosarcoma cell line. TGF-beta was not found to act as a general stimulator of small proteoglycan biosynthesis. In both cell types, an increased expression of the core protein of proteoglycan I was found. However, there was a profound decrease in the expression of a 106 kDa core protein, and either no alteration or a small decrease in the biosynthesis of the collagen-binding small proteoglycan II core protein. These results show that the production of individual members of the small proteoglycan family is differentially regulated.
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PMID:Non-uniform influence of transforming growth factor-beta on the biosynthesis of different forms of small chondroitin sulphate/dermatan sulphate proteoglycan. 220 Dec 87

The effects of interleukin 1, transforming growth factor-beta (coupling factors), prostaglandin E1, and prostaglandin E2 on incorporation of 45Ca2+ and on alkaline phosphatase activity were studied using cultured ROS 17/2.8 cells, one of cell lines derived from rat osteosarcoma. We found that all these factors stimulate both the incorporation of 45Ca2+ and alkaline phosphatase activity of these cells. On the other hand, one of the bone resorption hormones, parathyroid hormone (PTH), suppressed the proliferation of cells and decreased the alkaline phosphatase activity at considerably low concentrations (1 X 10(-12)-1 X 10(-11) M). However, the hormone stimulated the incorporation of 45Ca2+ by these cells in a dose-dependent manner; the maximum stimulation on day 3 was observed at 1 X 10(-7) M and it was approximately 3 times the control value. The data suggest therefore, that the osteoblasts incorporated calcium ions and transported them while bone resorption was occurring. Thus the ROS 17/2.8 cell line appears to be an advantageous experimental system for the study of calcium metabolism of osteoblasts in vitro.
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PMID:[Effects of various factors involved in bone metabolism on 45Ca2+ incorporation and alkaline phosphatase activity of ROS 17/2.8 cells]. 260 4

We report for the first time the bifunctional effects of transforming growth factor-beta on the growth of cloned human osteosarcoma cells (Htb96). Cell growth was assessed by determining the cell number, replication index and [3H]-thymidine incorporation following 48 hours incubation of cultured Htb96 cells with the peptide. Exposure of cells to concentrations of TGF-beta upto 40 pM caused a mitogenic response, concentrations between 40 and 800 pM failed to stimulate cell growth and higher doses caused an inhibition of cell proliferation. The initial cell density was found to alter the responsiveness of Htb96 cells to TGF-beta; stimulation of proliferation was less profound at high and low cell densities. The observed cell density- and growth factor concentration-dependent effects of TGF-beta on the growth of tumour cells might suggest the existence of an autocrine regulatory mechanism. Furthermore, by demonstrating a sensitivity to inhibition by indomethacin, we conclude that the proliferative effect of TGF-beta is at least, in part, dependent on the de novo synthesis of prostaglandins.
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PMID:Transforming growth factor-beta-induced mitogenesis of human bone cancer cells. 273 16

High specific activity estradiol labeled with iodine-125 was used to detect approximately 200 saturable, high-affinity (dissociation constant approximately equal to 1.0 nM) nuclear binding sites in rat (ROS 17/2.8) and human (HOS TE85) clonal osteoblast-like osteosarcoma cells. Of the steroids tested, only testosterone exhibited significant cross-reactivity with estrogen binding. RNA blot analysis with a complementary DNA probe to the human estrogen receptor revealed putative receptor transcripts of 6 to 6.2 kilobases in both rat and human osteosarcoma cells. Type I procollagen and transforming growth factor-beta messenger RNA levels were enhanced in cultured human osteoblast-like cells treated with 1 nM estradiol. Thus, estrogen can act directly on osteoblasts by a receptor-mediated mechanism and thereby modulate the extracellular matrix and other proteins involved in the maintenance of skeletal mineralization and remodeling.
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PMID:Estrogen binding, receptor mRNA, and biologic response in osteoblast-like osteosarcoma cells. 316 26

Fifteen archival human osteosarcoma specimens were examined by in situ hybridization for the expression of human and mouse transforming growth factor-beta (isoforms 1, 2, and 3), c-fos, and metalloproteinase (stromelysin-3 and matrilysin). Osteosarcoma subtypes were confirmed by review of patients' radiographs, histopathology, and age at diagnosis. The outcome and method of treatment were documented. The subtypes of osteosarcoma consisted of nine conventional osteosarcomas and two each of fibroblastic, telangiectatic, and post-radiation osteosarcomas. Each specimen was histologically examined under light microscopy, and then adjacent paraffin sections were assayed with sense and anti-sense RNA probes by in situ hybridization. The probes localized to the neoplastic cells, confirming the methodology of the technique. Human transforming growth factor-beta 1 had the most uniform binding affinity to the osteosarcomas examined and was more specific in binding than mouse transforming growth factor-beta 1. Specific mRNA encoding for the transforming growth factor-beta s, c-fos, and metalloproteinases are detectable in patterns within osteosarcoma cells, and collectively, their expression parallels the different histopathologic subtypes. The less differentiated subtypes (telangiectatic and post-radiation osteosarcomas) expressed the fewest molecular markers. Osteosarcoma is a heterogeneous tumor. Differential expression of matrilysin in osteosarcoma is the first reported detection of metalloproteinase activity in human skeletal sarcoma.
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PMID:Osteosarcoma oncogene expression detected by in situ hybridization. 747 45


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