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)

U-2 OS osteosarcoma cells are mesenchymal-derived transformed cells spontaneously expressing both platelet-derived growth factor (PDGF) A- and B-chain genes, and releasing PDGF AA dimers in culture. Using modified Boyden chemotactic chambers, platelet-purified PDGF was shown to be a chemoattractant for U-2 OS cells. More specifically, U-2 OS cells migrated in the presence of PDGF AB and BB dimers but not in the presence of PDGF AA dimers. This pattern of response was similar to that observed with human fibroblasts and this similarity is consistent with the fact that U-2 OS cells express PDGF receptor alpha- and beta-subunits in a similar fashion to human fibroblasts.
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PMID:Differential migratory response of U-2 OS osteosarcoma cell to the various forms of platelet-derived growth factor. 131 74

Epidermal growth factor (EGF), platelet-derived growth factor (PDGF), and heparin-binding growth factor-1 (HBGF-1) stimulated the proliferation of a variant of the human osteosarcoma cell line, MG-63-LS (LS = low serum). Transforming growth factor beta (TGF-beta) completely inhibited cell growth in basal medium supplemented with 2% fetal calf serum (FCS), blocked PDGF- and EGF-stimulated cell proliferation, and modulated that of HBGF-1. PDGF, but not EGF or HBGF-1, activated the inositol trisphosphate/diacylglycerol (IP3/DAG) second message system in a dose-dependent manner. EGF inhibited phosphoinositol lipid turnover and HBGF-1 and TGF-beta stimulated phosphatidylinositol hydrolysis to produce inositol phosphate (IP) but not IP3. Preincubation of quiescent cells with TGF-beta for 30-40 minutes prior to the addition of PDGF resulted in an inhibition of PDGF-induced production of IP3. This suggested that TGF-beta was an indirect inhibitor and blocked PDGF-stimulated cell growth in part by interfering with the generation of the second messenger, IP3.
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PMID:TGF-beta inhibits the platelet-derived growth factor-induced formation of inositol trisphosphate in MG-63 human osteosarcoma cells. 170 69

Platelet-derived growth factor (PDGF) is a potent mitogen for cells of mesenchymal origin. We previously demonstrated that PDGF is produced by osteogenic sarcoma cells. We report here that normal human bone-derived cells produce PDGF and that these cells have an osteoblastic phenotype. This was demonstrated by use of a double immunofluorescent technique and by examining cloned human adult osteoblasts. Northern blot analysis indicates that PDGF production is accounted for by expression of the PDGF-A gene. PDGF-AA and PDGF-BB generally stimulated thymidine incorporation in normal human bone explants to a similar extent. All of the cloned human osteoblasts responded to PDGF-BB while the response to PDGF-AA varied. Similarly, five cloned osteoblastic cell populations were shown to produce PDGF while one did not. This result supports the hypothesis that there are different osteoblastic cell populations that differ in their growth factor responses or in the production of growth factors. Our results suggest that PDGF-BB has the potential to act as a paracrine factor for normal human osteoblasts because all of the osteoblastic cell populations responded to PDGF-BB. None of the osteoblastic cell populations expressed the PDGF-B gene, indicating that it would not act as an autocrine factor. Although not definitive, our results suggest that PDGF-AA has the potential to act as an autocrine factor because osteoblastic bone cell populations were shown to express the PDGF-A gene and respond to PDGF-AA.
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PMID:Human osteoblasts synthesize and respond to platelet-derived growth factor. 183 27

The effect of alpha-tocopherol (vitamin E) on the proliferation of vascular smooth muscle cells (A7r5), human osteosarcoma cells (Saos-2), fibroblasts (Balb/3T3), and neuroblastoma cells (NB2A) has been studied. The proliferation of vascular smooth muscle cells was inhibited by physiologically relevant concentrations of alpha-tocopherol, neuroblastoma cells were only sensitive to higher alpha-tocopherol concentrations, and proliferation of the other cell lines was not inhibited. The inhibition of smooth muscle cell proliferation was specific for alpha-tocopherol. Trolox, phytol, and alpha-tocopherol esters had no effect. Proliferation of smooth muscle cells stimulated by platelet-derived growth factor or endothelin was completely sensitive to alpha-tocopherol. If smooth muscle cells were stimulated by fetal calf serum, proliferation was 50% inhibited by alpha-tocopherol. No effect of alpha-tocopherol was observed when proliferation of smooth muscle cells was stimulated by bombesin and lysophosphatidic acid. The possibility of an involvement of protein kinase C in the cell response to alpha-tocopherol was suggested by experiments with the isolated enzyme and supported by the 2- to 3-fold stimulation of phorbol ester binding induced by alpha-tocopherol in sensitive cells. Moreover, alpha-tocopherol also caused inhibition of protein kinase C translocation induced by phorbol esters and inhibition of the phosphorylation of its 80-kDa protein substrate in smooth muscle cells. A model is discussed by which alpha-tocopherol inhibits cell proliferation by interacting with the cytosolic protein kinase C, thus preventing its membrane translocation and activation.
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PMID:Inhibition of cell proliferation by alpha-tocopherol. Role of protein kinase C. 200 76

Tumor cells may stimulate their own proliferation through an autocrine mechanism by simultaneously producing growth factors and growth factor receptors. We now report that numerous human tumor-derived cell lines simultaneously express the genes for platelet-derived growth factor (PDGF) A and B chains and the PDGF receptor (PDGF-R). Measurement of mRNA transcribed from these genes showed that among 16 malignant glioma cell lines tested, 15 expressed the PDGF A gene, 12 expressed the PDGF B gene, and 13 expressed the PDGF-R gene. Of three osteosarcoma lines, three expressed PDGF A, two expressed PDGF B, and three expressed PDGF-R. For eight malignant melanoma lines, seven expressed PDGF A, five expressed PDGF B, and three expressed PDGF-R genes. Thus, 13 of 16 malignant glioma, 3 of 3 osteosarcomas, and 3 of 8 malignant melanoma cell lines expressed the PDGF receptor gene and either or both PDGF genes. Five cell lines were tested for production of biologically active PDGF and PDGF receptor protein. Media conditioned by each of the five cell lines induced tyrosine phosphorylation of a protein identical in size to the PDGF receptor. These five cell lines also produced PDGF receptor protein as measured by Western blot analysis or metabolic labeling and immunoprecipitation using PDGF-R antibodies. The PDGF receptors of these cell lines were activated by human platelet PDGF or by recombinant AA or BB homodimers. Intracellular interaction of these receptors with the growth factor simultaneously produced may provide continuous stimulation to the proliferation of these cells.
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PMID:Platelet derived growth factor (PDGF) autocrine components in human tumor cell lines. 215 59

The polyanionic compound suramin is currently being evaluated for antineoplastic activity. On the basis of previous in vitro studies, it has been suggested that the mechanism of action of suramin may be related to its ability to attenuate the mitogenic effects of peptide growth factors, such as platelet-derived growth factor and epidermal growth factor. We recently reported that MG-63 human osteosarcoma cells are mitogenically responsive to insulinlike growth factor I (IGF-I). We now demonstrate for the first time that suramin interferes with the interaction between IGF-I and its receptor and abolishes in vitro IGF-I-stimulated proliferation of these osteosarcoma cells. The fact that cell proliferation resumes when suramin is removed indicates that this is not a cytotoxic effect. We conclude that IGF-I should be added to the list of growth factors whose bioactivity can be attenuated by suramin and that clinical studies of suramin and its analogues are indicated in IGF-I-receptor-positive malignancies such as osteogenic sarcoma.
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PMID:Suramin blockade of insulinlike growth factor I-stimulated proliferation of human osteosarcoma cells. 216 71

The platelet-derived growth factor (PDGF) modulated growth response of the MG-63 human osteosarcoma cell line, which neither expresses c-sis mRNA nor secretes a PDGF analogue, was characterized. Scatchard analysis demonstrated that the MG-63 cells have 23,000 receptors per cell with a Kd of 5 X 10(-11) M. The receptor became phosphorylated, in a PDGF concentration-dependent manner, when 32P-orthophosphate-labeled cells were treated with PDGF for 3 h at 4 degrees C. The phosphorylated receptor was identified by autoradiography and gel electrophoresis after isolation of the 32P-labeled receptor using a solid-phase monoclonal antibody directed against phosphotyrosine. Binding of the receptor to the antibody was inhibited by 5 mM phenyl phosphate, further suggesting that PDGF stimulated tyrosine-specific receptor autophosphorylation. In addition, treatment of MG-63 cells with PDGF for 3 h at 37 degrees C induced a 7.5-fold increase in c-myc mRNA accumulation as analyzed on Northern gels. However, MG-63 cells grew equally well in either serum-(which contains PDGF) or plasma-(which does not) supplemented medium. Furthermore, PDGF did not stimulate DNA synthesis in growth arrested MG-63 cells, nor did it potentiate DNA synthesis modulated by somatomedin C. Thus MG-63 cells are a naturally occurring cell variant in which PDGF stimulates c-myc expression but does not modulate mitogenesis.
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PMID:PDGF induces c-myc mRNA expression in MG-63 human osteosarcoma cells but does not stimulate cell replication. 243 22

We examined several characteristics of the mitogenic activity of extracts of human prostatic adenocarcinoma and human benign prostatic hyperplasia in fetal rat calvarial cells, cloned rat osteosarcoma cells and rat skin fibroblasts. Prostatic moieties produced maximal stimulation of [3H]thymidine incorporation at 24 h, were mitogenic in the absence or presence of various concentrations of serum, and were active in calvarial cells enriched with osteoblasts, skin fibroblasts and the cloned rat osteosarcoma cell line UMR 108. The known growth-promoting agents insulin, insulin-like growth factor, fibroblast growth factor, platelet-derived growth factor, epidermal growth factor, interleukin-1 alpha and beta and transforming growth factor beta were also mitogenic in the indicator systems employed; however, maximally stimulating effects of these peptides in cells of the osteoblast phenotype were further enhanced with prostatic material. Prostatic activity was acid-stable and could be enriched with respect to osteoblast stimulation by hydrophobic and carboxymethyl ion-exchange chromatography. The results demonstrate the presence of potent mitogenic activity in hyperplastic and malignant prostatic tissue which appears to include unique osteoblast-stimulating activity.
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PMID:Effects of human prostatic mitogens on rat bone cells and fibroblasts. 245 Sep 42

We previously demonstrated that a high-molecular-weight glycoprotein could be immunoprecipitated from metabolically labeled U-2 OS cells with platelet-derived growth factor (PDGF) antiserum and that it appears to be derived from a different precursor than is the 30 kD PDGF-like mitogen produced by these cells. These findings were unexpected, since the molecular weight of this glycoprotein is too large to be encoded by the PDGF structural genes. From experiments with metabolically labeled U-2 OS human osteosarcoma, fibroblasts, and NRK cells, we report here that a 185 kD protein immunoprecipitated with PDGF antiserum has the following characteristics. 1) It is a PDGF binding protein that is unrelated to alpha 2-macroglobulin. 2) It is phosphorylated in response to PDGF stimulation. 3) It is immunoprecipitated by phosphotyrosine antibodies. 4) It is not a substrate of epidermal growth factor-induced tyrosine kinase activity. These studies indicate that high-molecular-weight proteins immunoprecipitated by antiserum to PDGF represent a complex between PDGF and a binding protein capable of being phosphorylated by a PDGF-induced tyrosine kinase. These characteristics are identical to those of the PDGF receptor.
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PMID:Characterization of a high-molecular-weight protein immunoprecipitated by platelet-derived growth factor antisera. 246 74

The growth of MG63 human osteosarcoma cell line in 5% serum is stimulated by epidermal growth factor (EGF), platelet-derived growth factor (PDGF), or heparin-binding growth factor-1 (HBGF-1). The mitogenic effect of EGF and PDGF is completely blocked by TFG-beta at 1 ng per ml and the effect of HBGF-1 is attenuated by 75-80%. Treatment of MG63 cells with TGF-beta reduces HBGF-1 receptor binding affinity from 1.24 x 10(-11) M to 3.51 x 10(-11) M with no change on the receptor number (1.1 x 10(3) per cell). The receptor-binding affinity of EGF and PDGF is not altered by TGF-beta treatment; however, the number of EGF receptor is increased by 25%. Both EGF and PDGF stimulate MG63 cellular tyrosine kinase activity, and such stimulation is inhibited by TGF-beta pretreatment. No change in the cellular protein tyrosine phosphorylation pattern can be detected in HBGF-1-stimulated cells with and without TGF-beta pretreatment. These data suggest that TGF-beta inhibits EGF and PDGF mitogenicity by blocking EGF- and PDGF-stimulated tyrosine kinase activity and attenuates HBGF-1 mitogenicity by decreasing its receptor affinity.
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PMID:Differential inhibitory effects of TGF-beta on EGF-, PDGF-, and HBGF-1-stimulated MG63 human osteosarcoma cell growth: possible involvement of growth factor interactions at the receptor and postreceptor levels. 247 12


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