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)

Bromodeoxyuridine (BrdU) labeled human prostatic cancer cells, PC-3, and murine osteosarcoma cells, POS-1 were injected into the tail veins of male mice under concomitant temporal occlusion of inferior vena cava. Five minutes after release of the venous occlusion, animals were sacrificed and various tissues, organs and the vertebral bones were examined immunohistochemically using an application of BrdU-anti-BrdU methods. Obvious BrdU labeled tumor cells, isolated or clumped, were demonstrated within the venous channels along the vertebral column, the epidural venous channels around spinal nervous tissues, in the bone marrow of lumbo-sacral vertebrae and intra- and peri-prostatic venous channels. The results suggest that a blockade of short duration of venous flow at the inferior vena cava can result in the bypassing of tumor cells through the vena cava to the vertebral venous system, which has a close connection with the peri-prostatic venous plexus. Thus, the vertebral venous system may play an important role in the metastasis of prostatic carcinoma to bone. In addition this experimental procedure is a very valuable model for studying mechanisms and prevention of bone metastases from prostatic carcinoma.
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PMID:Role of the vertebral venous system in metastatic spread of cancer cells to the bone. 149 28

Prostatic cancer is frequently associated with new bone formation although the tumor-derived factors responsible for changes in bone cell function have not been identified. We have examined the synthesis of osteoblast-stimulating factors in a cultured human prostatic cancer cell line (PC-3) and show that conditioned medium from PC-3 cells stimulate mitogenesis and alkaline phosphatase in cells with the osteoblast phenotype (cultured rat osteosarcoma cells) and collagen synthesis in fetal rat calvaria. In order to characterize tumor-derived gene products which stimulate cells of the osteoblast phenotype messenger RNA (mRNA) was isolated from PC-3 cells and microinjected into Xenopus laevis oocytes. mRNA-directed translation products which were secreted into the oocyte medium were collected and assayed for a number of osteoblast stimulating properties. Translation products from PC-3 mRNA-injected oocytes stimulated division of cultured osteosarcoma cells by 8-fold and increased DNA synthesis as measured by incorporation of [3H]thymidine into these cells. In addition, tumor-derived translation products stimulated the production of alkaline phosphatase activity, a marker enzyme for bone formation, in cultured osteosarcoma cells. Oocytes injected either with water or with mRNA from a tumor not associated with bone formation were devoid of these activities. Total mRNA from the human prostatic cancer cells was then denatured and fractionated by size by agarose gel electrophoresis. When individual fractions of mRNA were eluted from the gel, translated in Xenopus oocytes, and the secreted translation products were tested for alkaline phosphatase-stimulating activity on osteoblast-like cells, the majority of the activity could be recovered in a mRNA fraction which was approximately 1800 bases in length. These results indicate that the PC-3 prostatic cancer cell line synthesizes a mRNA of approximately 1800 bases which codes for a heretofore unrecognized osteoblast-stimulating factor.
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PMID:Identification of a messenger ribonucleic acid fraction in human prostatic cancer cells coding for a novel osteoblast-stimulating factor. 386 13

We have examined expression of bone morphogenetic protein 3 (BMP-3) mRNA in normal rat osteoblasts in culture as they undergo differentiation to form bone-like structures, and have found that expression of BMP-3 mRNA in primary fetal rat calvarial (FRC) cells is discontinuous and shows at least four different-sized transcripts. BMP-3 mRNA expression has a distinct temporal pattern during bone cell differentiation of FRC osteoblasts. Previously, we showed that BMP-3 mRNA is expressed in normal and neoplastic rat and human prostate tissues, and in human osteosarcoma cells, as multiple transcripts. To compare the nature of these transcripts in different tissues, three cDNA clones encoding BMP-3 have been isolated by reverse transcription-polymerase chain reaction (RT-PCR) and cDNA library screening from human prostate cancer PC-3 cells, rat prostate adenocarcinoma PA III cells, and primary FRC cells. Analysis of these clones has revealed that the nucleotide sequence of BMP-3 found in human prostate cells is identical to that found in human bone cells. The rat BMP-3 sequences from bone and prostate cells are also identical but show a high degree of variation in the pro- or precursor region compared with human BMP-3. The biological significance of these differences in these two species is unknown.
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PMID:Sequence and expression of bone morphogenetic protein 3 mRNA in prolonged cultures of fetal rat calvarial osteoblasts and in rat prostate adenocarcinoma PA III cells. 788 Apr 44

We investigated the ability of important regulators of osteoblast function, such as insulin-like growth factor I (IGF-I), transforming growth factor beta 1 (TGF beta 1), and urokinase-type plasminogen activator (uPA) to act as mediators in cell-cell interactions between osteoblast-like cells and metastatic prostate cancer cells, in vitro. In addition, we assessed whether these growth substances can (a) mediate glucocorticoid receptor (GR) function and (b) be implicated in dexamethasone-induced regression of osteoblastic tumors. Exogenous IGF-I, rat/human uPA, and PA-III (rat)/PC-3 (human) prostate cancer cells conditioned media (CM) stimulated the proliferation of rat (UMR 106 cells) and human (MG-63 cells) osteosarcoma cells. This mitogenic activity was completely neutralized by anti-IGF-I specific antibody. In addition, dexamethasone decreased cell growth, up regulated TGF beta 1 mRNA, and down regulated uPA mRNA expression in prostate cancer cells. Furthermore, it inhibited cell growth by activating latent-TGF beta 1 in osteoblast-like cells. In addition, dexamethasone down regulated the expression of IGF-I mRNA in osteoblast-like cells. Therefore, it is conceivable that uPA, TGF beta 1 and IGF-I mediate at least in part cell-cell interactions and GR function in osteoblastic metastases. Conceivably, regression of the osteoblastic tumors produced by high-dose dexamethasone treatment in hormone-refractory prostate cancer patients is been mediated by differential regulation of growth factors, locally.
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PMID:Growth factors mediate glucocorticoid receptor function and dexamethasone-induced regression of osteoblastic lesions in hormone refractory prostate cancer. 917 84

Human prostatic carcinoma frequently metastasizes to bone tissue and activates bone metabolism, especially bone formation, at the site of metastasis. It has been reported that an extract of prostatic carcinoma and conditioned medium (CM) of a human prostatic carcinoma cell line, PC-3, established from a bone metastastic lesion, stimulate osteoblastic cell proliferation. However, there is little information about the effect of PC-3 CM on the differentiation of osteoblastic cells. In this study, we investigated the effect of PC-3 CM on the differentiation of two types of osteoblastic cells, primary fetal rat calvaria (RC) cells containing many undifferentiated osteoprogenitor cells, and ROS 17/2.8, a well-differentiated rat osteosarcoma cell line. PC-3 CM inhibited bone nodule formation and the activity of alkaline phosphatase (ALPase), an osteoblastic marker enzyme, on days 7, 14, and 21 (RC cells) or 3, 6, and 9 (ROS 17/2.8 cells) in a dose-dependent manner (5-30% CM). However, the CM did not affect cell proliferation or cell viability. PC-3 CM was found to markedly block the gene expression of ALPase and osteocalcin (OCN) mRNAs but had no effect on the mRNA expression of osteopontin (OPN), the latter two being noncollagenous proteins related to bone matrix mineralization. These findings suggest that PC-3 CM contains a factor that inhibits osteoblastic cell differentiation and that this factor may be involved in the process of bone metastasis from prostatic carcinoma.
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PMID:Inhibition of osteoblastic cell differentiation by conditioned medium derived from the human prostatic cancer cell line PC-3 in vitro. 932 30

Our laboratory has developed two cellular models of human prostate cancer progression. The LNCaP prostate cancer progression model is based upon the well-known cellular interaction between human prostate or bone stromal cells and LNCaP cells in vivo. The marginally tumorigenic LNCaP cells acquired tumorigenic and metastatic potential upon cellular interaction with either prostate or bone fibroblasts. A subline termed C4-2 was observed to grow readily in castrated animals and acquired metastatic potential spreading from the primary tumor site to the lymph node, the seminal vesicles, and the axial skeleton, resulting in an intense osteoblastic reaction. The second model is ARCaP, where prostate cancer cells derived from the ascites fluid of a man with metastatic disease exhibited an Androgen- and estrogen-Repressed Prostate Cancer cell growth and tumor formation in either a hormone-deficient or a castrated environment. However, the growth of either the tumor cells in vitro or the tumors in vivo was suppressed by both estrogen and androgen. While the tumor cells expressed low levels of androgen receptor and prostate-specific antigen (PSA), they were highly metastatic when inoculated orthotopically. Distant metastases to a number of organs were detected, including the liver, lung, kidney, and bone. We have employed a human prostate cancer progression model as a system to study the efficacy of gene therapy. Results of the study show that whereas universal promoters, such as Cytomegalovirus (CMV) and Rous Sarcoma Virus (RSV) promoter-driven tumor suppressors (e.g. p53, p21, and p16), were effective in inhibiting prostate tumor growth, the advantages of driving the expression of therapeutic toxic genes using a tissue-specific promoter prostate-specific antigen (PSA) and a tumor--but not tissue-specific promoter, osteocalcin (OC), are preferred. In the case of the PSA promoter, we can achieve cell-kill in PSA-producing human prostate cancer cells. To circumvent the supporting role of bone stroma for prostate cancer epithelial growth, we have recently developed a novel concept where the expression of therapeutic toxic genes is driven by a tumor--but not a tissue-specific OC promoter. Osteocalcin-thymidine kinase (OC-TK) was found to efficiently eradicate the growth of osteosarcoma, prostate, and brain tumors both in vitro and in vivo. We observed that androgen-independent human prostate cancer cells lines expressed OC-TK at higher levels than androgen-dependent human prostate cancer cell lines. We have obtained data to suggest that Ad-OC-TK plus a pro-drug acyclovir (ACV) may be used as an effective therapy to treat prostate cancer bone metastasis in models where the growth of androgen-independent PC-3 and C4-2 tumors in the bone has occurred.
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PMID:Human prostate cancer progression models and therapeutic intervention. 943 28

Bone metastases are a common complication in prostate and breast cancer patients. It leads to extensive morbidity and eventually mortality. Matrix metalloproteinases (MMPs) are known to be involved in the metastatic process. MMP activity can be down-regulated by transforming growth factor beta1 (TGF-beta1), a growth-modulating factor, found in high concentrations in the bone. TGF-beta1 acts through the TGF-beta1 inhibitory element (TIE) element, a cis-acting element found in the promoter region of most MMP genes, with the exception of MMP-2. We used three human cell lines relevant for bone metastases, namely prostate adenocarcinoma PC-3, breast adenocarcinoma MDA-MB-231, and adenocarcinoma cells of unknown origin, Hs696, and one human osteosarcoma cell line, SAOS-2, and showed that in these cell lines TGF-beta1 partially lost its repressing action on MMP expression. TGF-beta1 was able to induce MMP-9 activity and protein expression in all three bone-metastatic tumour cell types, whereas MMP-9 protein levels were repressed in SAOS-2 cells. In PC-3 cells, TGF-beta1 repressed MMP-1 expression, whereas in MDA-MB-231 and SAOS-2 cells, an increase in the expression of MMP-1 protein was detected. Additionally, an increase in MMP-3 expression was observed in Hs696 cells. Expression and activity of the tissue inhibitors of matrix metalloproteinases, TIMP-1 and TIMP-2, were found increased in both PC-3 and MDA-MB-231 cells. With respect to cell proliferation, TGF-beta1 was able to induce a dose-dependent growth inhibition of up to 50% in primary human mammary epithelial cells. However, in none of the tumour cell lines was TGF-beta1 able to suppress growth substantially. Data presented in this paper support the hypothesis that TGF-beta1 can potentially disrupt the balance existing between osteoclast- and osteoblast-derived MMP activity by inducing altered expression of matrix metalloproteinases and their tissue inhibitors derived from bone-metastasizing cancer cells. This could eventually lead to skeletal destruction in patients with advanced metastatic disease.
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PMID:Transforming growth factor beta1 acts as an inducer of matrix metalloproteinase expression and activity in human bone-metastasizing cancer cells. 1039 Jan 44

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

A 70% methanol extract of Terminalia chebula fruit, was studied for its effects on growth in several malignant cell lines including a human (MCF-7) and mouse (S115) breast cancer cell line, a human osteosarcoma cell line (HOS-1), a human prostate cancer cell line (PC-3) and a non-tumorigenic, immortalized human prostate cell line (PNT1A) using assays for proliferation ([(3)H]-thymidine incorporation and coulter counting), cell viability (ATP determination) and cell death (flow cytometry and Hoechst DNA staining). In all cell lines studied, the extract decreased cell viability, inhibited cell proliferation, and induced cell death in a dose dependent manner. Flow cytometry and other analyses showed that some apoptosis was induced by the extract at lower concentrations, but at higher concentrations, necrosis was the major mechanism of cell death. ATP assay guided chromatographic fractionation of the extract yielded ellagic acid, 2,4-chebulyl-beta-D-glucopyranose (a new natural product), and chebulinic acid which were tested by ATP assay on HOS-1 cell line in comparison to three known antigrowth phenolics of Terminalia, gallic acid, ethyl gallate, luteolin, and tannic acid. Chebulinic acid (IC(50) = 53.2 microM +/- 0.16) > tannic acid (IC(50) = 59.0 microg/ml +/- 0.19) > and ellagic acid (IC(50) = 78.5 microM +/- 0.24), were the most growth inhibitory phenolics of T. chebula fruit in our study.
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PMID:Inhibition of cancer cell growth by crude extract and the phenolics of Terminalia chebula retz. fruit. 1212 33

The hypothesis that glucose deprivation-induced cytotoxicity in transformed human cells is mediated by mitochondrial O2*- and H2O2 was first tested by exposing glucose-deprived SV40-transformed human fibroblasts (GM00637G) to electron transport chain blockers (ETCBs) known to increase mitochondrial O2*- and H2O2 production (antimycin A (AntA), myxothiazol (Myx), or rotenone (Rot)). Glucose deprivation (2-8 h) in the presence of ETCBs enhanced parameters indicative of oxidative stress (i.e. GSSG and steady-state levels of oxygen-centered radicals) as well as cytotoxicity. Glucose deprivation in the presence of AntA also significantly enhanced cytotoxicity and parameters indicative of oxidative stress in several different human cancer cell lines (PC-3, DU145, MDA-MB231, and HT-29). In addition, human osteosarcoma cells lacking functional mitochondrial electron transport chains (rho0) were resistant to glucose deprivation-induced cytotoxicity and oxidative stress in the presence of AntA. In the absence of ETCBs, aminotriazole-mediated inactivation of catalase in PC-3 cells demonstrated increases in intracellular steady-state levels of H2O2 during glucose deprivation. Finally, in the absence of ETCBs, overexpression of manganese containing superoxide dismutase and/or mitochondrial targeted catalase using adenoviral vectors significantly protected PC-3 cells from toxicity and oxidative stress induced by glucose deprivation with expression of both enzymes providing greater protection than was seen with either alone. Overall, these findings strongly support the hypothesis that mitochondrial O2*- and H2O2 significantly contribute to glucose deprivation-induced cytotoxicity and metabolic oxidative stress in human cancer cells.
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PMID:Mitochondrial O2*- and H2O2 mediate glucose deprivation-induced stress in human cancer cells. 1556 20


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