Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of interleukin-1 (IL-1 alpha or IL 1 beta) on androgen-dependent LNCaP and androgen-independent JCA-1 human prostatic cancer cell proliferation were investigated. IL-1 alpha or IL-1 beta induced a dose dependent growth reduction by 50-80% as determined by cell cycle phase distribution, cell number and clonal growth in short and long term cultures. IL-1 negated the androgen growth effect on equal molar basis but the androgen receptors were not blocked by IL-1. The presence of intracellular IL-1 receptors was detected by flow cytometry and the IL-1 mediated growth reduction could be blocked with a 500 fold excess of the IL-1 receptor antagonist (hIL-1ra), revealing a growth control involving IL-1, HIL-1ra, androgen and their receptors.
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PMID:Growth modulation of human prostatic cancer cells by interleukin-1 and interleukin-1 receptor antagonist. 765 19

We have identified a new antiproliferative activity from the conditioned medium of two androgen-independent prostatic cancer cell lines, PC3 and DU-145. This antiproliferative activity selectively inhibited cell proliferation of an androgen-dependent prostate cancer cell line LNCaP in a dose-dependent manner. No antiproliferative activity was observed against mouse fibroblast 3T3, normal human lymphocytes, human leukemic cells, including promyelocyte HL-60 or T cell HUT-78, or human adenocarcinoma cell lines, including prostatic cells JCA-1, ovary NIH:OVCAR-3, cervix C-33A, or breast MDA-MB-231. Cell cycle analysis revealed that the antiproliferative activity did not induce apoptosis in LNCaP cells, but it prevented some G1 LNCaP cells from entering into the S phase of the cell cycle. The antiproliferative activity was sensitive to high temperature (100 degrees C) and to proteinase digestion; however, it was resistant to 56 degrees C, pH 2.0, and reducing agent treatment, as well as to DNase and RNase digestion. The antiproliferative activity was partially purified by gel filtration, ion-exchange chromatography, and SDS-PAGE, with an apparent molecular weight of 50 kD. The antiproliferative activity was not affected by neutralizing antibody against TGF-beta 1,2,3, TNF-alpha, PDGF, EGF, IL-1, IL-2, IL-3, IL-4, or IL-6.
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PMID:Antiproliferative effect of a prostatic cell-derived activity on the human androgen-dependent prostatic carcinoma cell line LNCaP. 859 Mar 22

Cancer is consistently associated with anorexia. The Lobund-Wistar rat model of prostate cancer exhibits clinical manifestations (including anorexia) that resemble many aspects of the human disease. Cytokines are proposed to be involved in cancer-associated anorexia. Here we investigated mRNA profiles of feeding-modulatory cytokines and neuropeptides in specific brain regions of anorectic Lobund-Wistar rats bearing prostate adenocarcinoma tumor cells. Interleukin (IL)-1beta system components (ligand, signaling receptor, receptor accessory proteins, receptor antagonist), tumor necrosis factor-alpha, transforming growth factor-beta1, glycoprotein 130 (IL-6 receptor signal transducer), proopiomelanocortin (POMC, opioid peptide precursor), and neuropeptide Y (NPY) mRNAs were analyzed with sensitive and specific RNase protection assays. The same brain region sample was assayed for all components. The data show that early anorexia in tumor-bearing rats was associated with an upregulation of IL-1beta mRNA in the brain regions examined (cerebellum, cortex, and hypothalamus). IL-1 receptor antagonist (IL-1Ra) mRNA and IL-1 receptor type I mRNA levels were also significantly increased in the cortex and hypothalamus. All other cytokine components, POMC, or NPY mRNA levels were not significantly different between tumor-bearing and pair-fed (control) rats. IL-1beta mRNA and IL-1Ra mRNA were also significantly upregulated in the spleen of tumor-bearing rats. These data suggest that 1) IL-1beta mRNA upregulation in the brain may be relevant to the anorexia exhibited by the tumor-bearing Lobund-Wistar rat and 2) in vivo characterization of cytokine components in discrete brain regions during cancer is necessary to understand underlying molecular mechanisms responsible for cancer-associated neurological manifestations.
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PMID:Brain cytokine mRNAs in anorectic rats bearing prostate adenocarcinoma tumor cells. 968 94

Growth and development of some prostate epithelial cells are androgen-dependent. Non-androgenic hormones and growth factors may also influence prostate cells and the effect of interleukin 1beta (IL-1beta) has been investigated with an androgen-dependent human prostate cancer cell line LNCaP. Exposure of LNCaP cells to IL-1beta at picomole ranges resulted in a dose-dependent and progressive differentiation to neuroendocrine-like cells evidenced by dendrite formation and the development of specific neuroendocrine cell markers. Quantification by computer-based image analysis after immunostaining revealed a two-fold increase of chromogranin A in 90% of the cells and a ten-fold increase in the remaining 10%. Additionally, serotonin was developed in all the cells with the staining intensity increased by five-fold. Significant increase in cytokeratin 8 and reduction of prostate specific antigen was also noted. Proliferation was reduced in parallel to the cellular development. The IL-1beta effect was irreversible after several days of IL-1beta incubation. IL-1beta is produced constitutively and its secreted level has an inversed relation during the exponential and plateau phases of cell growth. An IL-1 autocrine regulation in the growth and differentiation of prostate cells is discussed.
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PMID:Development of human prostate cancer cells to neuroendocrine-like cells by interleukin-1. 1053 89

Urokinase-type plasminogen activator (uPA) plays a central role in many aspects of cellular regulation, such as fibrinolysis, cell migration, and metastasis. The uPA induction by inflammatory stimuli such as IL-1, TNFalpha, and lipopolysaccharide (LPS) has been reported in a number of human cells. We examined the effects of LPS on uPA expression in human PC-3 prostatic cancer cells that express uPA in a conditioned medium. LPS increased the uPA accumulation in PC-3 cells, whereas IL-1, IL-6, and TNFalpha did not. Northern blot analysis revealed that the peak induction of uPA mRNA occurred 5 hours after LPS stimulation. A protein synthesis inhibitor, cycloheximide, amplified the LPS-induced uPA mRNA, suggesting that LPS induces uPA by activating the gene expression in which de novo protein synthesis is not necessary.
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PMID:Induction of urokinase-type plasminogen activator by lipopolysaccharide in PC-3 human prostatic cancer cells. 1070 10

Osteoprotegerin (OPG), a member of the tumor necrosis receptor family, is produced by various tissues and inhibits osteoclast differentiation and activity. Since the metastasis of prostate cancer to bone often induces osteosclerosis, the possibility that these tumor cells secrete OPG is of interest. We have investigated whether the prostate cancer cell lines LNCaP, PC-3, and DU-145 produce and secrete OPG in vitro and if the production might be regulated by cytokines involved in remodeling of bone. OPG transcripts were detected by RT-PCR in all cell lines. OPG in culture media was analyzed by ELISA. In all three lineages, treatment with tumor necrosis factor-alpha and interleukin-1 beta dose dependently (5-5000 pM) stimulated the OPG secretion. Treatment with tumor necrosis factor-beta in increasing concentrations (1-1000 pM) stimulated OPG secretion in PC-3 but had no effect on the DU-145 and LNCaP cells. Dexamethasone (100 pM) had a small, but not significant, inhibitory effect on OPG secretion from DU-145 and LNCaP. In human non-malignant prostate cells, used as controls, there was no effect of IL-1 or TNFs on the secretion rate of OPG.
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PMID:Osteoprotegerin secretion from prostate cancer is stimulated by cytokines, in vitro. 1205 22

Prostate adenocarcinoma is associated with the formation of osteoblastic metastases in bone. It is hypothesized that osteoclastogenesis is a critical component in the development of skeletal metastases. These findings, however, were generally noted in predominantly osteolytic lesions. The pathophysiology of osteoblastic lesions remains unknown but the type of bone lesion formed may be influenced by the cytokines produced by prostate tumors. To test this theory, we implanted PC-3 and LAPC-9 cells into the tibias of SCID mice. These mice were sacrificed at 1, 2, 4, 6, and 8 weeks after implantation and histologic analysis was performed on these tibias. PCR analysis was also performed on bulk tumors. The results showed that the PC-3 implanted tibias developed pure osteolytic lesions while the LAPC-9 implanted tibias developed pure osteoblastic lesions on radiographs. Analysis of tibias after injection with PC-3 cells revealed progressive osteolytic lesions with abundant osteoclast activity at 2 weeks and destruction of the proximal tibia at 6 weeks after cell implantation. In contrast, the LAPC-9 cells formed osteoblastic lesions six weeks after cell injection. There were rare osteoclasts prior to the establishment of the osteoblastic lesions but greater osteoclast activity was noted with remodeling of the osteoblastic lesion 8 weeks after implantation of the tumor cells. PCR analysis revealed that PC-3 cells produced RANKL, IL-1, and TNF-alpha, which are associated with osteoclastogenesis. In contrast, LAPC-9 cells produced osteoprotegerin, which blocks osteoclast production and no detectable levels of RANKL or IL-1 and only minimal amounts of TNF-alpha were noted. These cells secreted BMP-2, -4, -6, and IL-6, which are associated with bone formation. These results suggest that the role of the osteoclast in the development of a metastatic lesion is variable depending on the phenotype of the prostate cancer cells, and that tumor-induced osteolysis may not be required for osteoblastic metastases.
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PMID:Differences in the cytokine profiles associated with prostate cancer cell induced osteoblastic and osteolytic lesions in bone. 1250 81

Here, we describe that microenvironmental IL-1 beta and, to a lesser extent, IL-1 alpha are required for in vivo angiogenesis and invasiveness of different tumor cells. In IL-1 beta knockout (KO) mice, local tumor or lung metastases of B16 melanoma cells were not observed compared with WT mice. Angiogenesis was assessed by the recruitment of blood vessel networks into Matrigel plugs containing B16 melanoma cells; vascularization of the plugs was present in WT mice, but was absent in IL-1 beta KO mice. The addition of exogenous IL-1 into B16-containing Matrigel plugs in IL-1 beta KO mice partially restored the angiogenic response. Moreover, the incorporation of IL-1 receptor antagonist to B16-containing plugs in WT mice inhibited the ingrowth of blood vessel networks into Matrigel plugs. In IL-1 alpha KO mice, local tumor development and induction of an angiogenic response in Matrigel plugs was less pronounced than in WT mice, but significantly higher than in IL-1 beta KO mice. These effects of host-derived IL-1 alpha and IL-1 beta were not restricted to the melanoma model, but were also observed in DA/3 mammary and prostate cancer cell models. In addition to the in vivo findings, IL-1 contributed to the production of vascular endothelial cell growth factor and tumor necrosis factor in cocultures of peritoneal macrophages and tumor cells. Host-derived IL-1 seems to control tumor angiogenesis and invasiveness. Furthermore, the anti-angiogenic effects of IL-1 receptor antagonist, shown here, suggest a possible therapeutic role in cancer, in addition to its current use in rheumatoid arthritis.
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PMID:IL-1 is required for tumor invasiveness and angiogenesis. 1259 51

Prostate cancer metastasis to bone may be mediated by preferential proliferation of these cells in the bone's microenvironment. We hypothesize that this preferential proliferation is mediated by bone-associated growth factors (GFs) and cytokines. To test our hypothesis, human prostate cancer cells, derived from both soft tissue (LNCaP, DuCaP, DU145) and bone metastases (PC-3, VCaP, MDA-2a, MDA-2b), were treated with bone-associated GFs and cytokines (PDGF, IGF-1, TGF-beta, EGF, bFGF, TNF-alpha, IL-1, and IL-6) for 48 h, and their growth responses were compared. The responses of soft tissue-derived prostate cancer cell lines to bone GFs and cytokines were variable. LNCaP cell growth was stimulated by IGF-1 but was inhibited by TNF-alpha. DU145 cell growth was stimulated with EGF. Prostate cancer cell lines derived from bone metastases also responded variably to bone GFs and cytokines. IL-1 stimulated the growth of MDA-2a and 2b cell lines in a dose-dependent manner. PDGF and bFGF both demonstrated variable effects on bone-derived prostate cancer cell lines. TNF-alpha inhibited proliferation of the VCaP cells. These findings demonstrate that human prostate cancer cell lines derived from bone metastases may not respond preferentially to bone-associated GFs and cytokines.
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PMID:The effect of bone-associated growth factors and cytokines on the growth of prostate cancer cells derived from soft tissue versus bone metastases in vitro. 1263 88

Bisphosphonates are endogenous pyrophosphate analogs in which a carbon atom replaces the central atom of oxygen. They are indicated in non-neoplastic diseases including osteoporosis, corticosteroid-induced bone loss, Paget disease, and in cancer-related diseases such as neoplastic hypercalcemia, multiple myeloma and bone metastases secondary to breast and prostate cancer. There is now extensive in vitro evidence suggesting a direct antitumor effect of bisphosphonates at different levels of action. Some new in vitro and in vivo studies support the cytostatic effects of bisphosphonates on tumor cells, and the effects on the regulation of cell growth, apoptosis, angiogenesis, cell adhesion, and invasion, with particular attention to biological properties. Well designed clinical trials are necessary to investigate whether the antitumor potential of bisphosphonates may be clinically relevant. On the basis of their effects on macrophages, we may divide bisphosphonates into two distinct categories: aminobisphosphonates, which sensitize macrophages to an inflammatory stimulus inducing an acute-phase response, and non-aminobisphosphonates that can be metabolized into macrophages and that may inhibit the inflammatory response of macrophages. There is evidence of aminobisphosphonate-induced pro-inflammatory response, in particular, related to modifications of the cytokine network. Several in vivo studies have demonstrated an acute-phase reaction after the first administration of aminobisphosphonates, with a significant increase in the main pro-inflammatory cytokines. However, a peculiar aspect concerning the action of non-aminobisphosphonates seems to be an anti-inflammatory activity caused by the inhibition of the release of inflammatory mediators from activated macrophages, such as interleukin (IL)-6, tumor necrosis factor-alpha and IL-1. The inhibition of inflammatory responses is demonstrated in both in vivo and in vitro models. This activity suggests the use of non-aminobisphosphonates in several inflammatory diseases characterized by macrophage-mediated production of acute-phase cytokines, as prevention of erosions in rheumatoid arthritis, and of loosening of joint prostheses, as well as possibly in osteoarthritis, ankylosing spondylitis, myelofibrosis, and hypertrophic pulmonary osteoarthropathy.
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PMID:Bisphosphonate effects in cancer and inflammatory diseases: in vitro and in vivo modulation of cytokine activities. 1524 2


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