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)

Cell adhesion molecule expression has been linked to disease outcome in prostatic adenocarcinomas (PACs). We evaluated the coordinated expression of catenin-related proteins, E-cadherin, N-cadherin, and CD44s in PACs. Archival sections from 112 PACs were immunostained by an automated method (Ventana Medical Systems, Tucson, AZ) using monoclonal antibodies to alpha- and beta-catenins, p120CTN, E-cadherin, N-cadherin, and CD44s proteins. Immunoreactivity was semiquantitatively scored, and results were evaluated for association between these markers. Staining results were also correlated with tumor grade, stage, ploidy, preoperative serum PSA, and postoperative biochemical disease recurrence. Decreased expression of alpha- and beta- catenins, p120CTN, E-cadherin, and CD44s proteins (range, 5% to 49%) was noted in PACs, and downregulation of each of these proteins correlated with high tumor grade (P =.02 to.0001). Although loss of E-cadherin and p120CTN each correlated with stage (E-cadherin, P =.02; p120CTN, P =.02) and ploidy (E-cadherin, P =.0001; p120CTN, P =.004), downregulation of CD44s correlated with ploidy (P =.002), serum PSA (P =.005), and postoperative disease recurrence (P =.02). N-cadherin was positive in only 5% of PACs and did not correlate with any prognostic parameters. alpha-Catenin downregulation correlated with decreased expression of E-cadherin (P =.0001). Additionally, decreased expression of each of these 2 proteins respectively correlated with loss of beta-catenin (P =.0001 and.004), p120CTN (P =.005 and.001), and CD44s (P =.008 and.01). beta-Catenin expression levels correlated with p120CTN (P =.01). A trend for co-downregulation of CD44s and p120CTN and of CD44s and beta-catenin was observed. In conclusion, the significant association between decreased expression of various members of the CAM family of proteins supports their collective role in mediating cell-cell adhesion. Altered expression of these proteins may be of prognostic value in patients with prostate cancer.
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PMID:Co-downregulation of cell adhesion proteins alpha- and beta-catenins, p120CTN, E-cadherin, and CD44 in prostatic adenocarcinomas. 1152 Dec 30

We have previously shown that CEACAM1, a cell-adhesion molecule, acts as a tumor suppressor in prostate carcinoma. Expression of CEACAM1 in prostate cancer cells suppresses their growth in vivo. However, CEACAM1 has no effect on the growth of prostate cancer cells in vitro. This difference suggests that the antitumor effect of CEACAM1 may be due to inhibition of tumor angiogenesis, perhaps by increased secretion of antiangiogenic molecules from the cells. In this study, we have demonstrated that expression of CEACAM1 in DU145 prostate cancer cells induced the production of a factor or factors that specifically blocked the growth of endothelial but not epithelial cells. Conditioned medium from the CEACAM1-expressing cells but not control luciferase-expressing cells inhibited endothelial cell migration up a gradient of stimulatory vascular endothelial growth factor in vitro and inhibited corneal neovascularization induced by basic fibroblast growth factor in vivo. Moreover, conditioned medium from CEACAM1-expressing cells induced endothelial cell apoptosis in vitro. Only medium conditioned by CEACAM1 mutants that were able to suppress tumor growth in vivo could cause endothelial cell apoptosis. These observations suggest that CEACAM1-mediated tumor suppression in vivo is, at least in part, due to the ability of CEACAM1 to inhibit tumor angiogenesis.
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PMID:Inhibition of prostate tumor angiogenesis by the tumor suppressor CEACAM1. 1212 2

CD44 is a multifunctional cell surface adhesion molecule that has been implicated in tumour cell invasion and metastasis. Many cancer cell types as well as their metastases express high levels of CD44. Furthermore, the expression of certain CD44 variants has been linked with metastasis and tumour progression. It is known that ezrin, a member of the ERM family of proteins, can bind to CD44 and thus raises the possibility that it is involved in cell migration and metastasis. Therefore we examined the expression and distribution of CD44, its co-localisation and translocation with ezrin in prostate cancer cell lines as they interact with endothelial cells. Experimental results indicate prostate cancer cells express multiple CD44 isoforms that co-localise with ezrin in DU-145 and PC-3 prostate cancer cells. Treatment with hepatocyte growth factor (HGF/SF) resulted in up-regulation of CD44 and its co-translocation with ezrin during tumour-endothelial cell interactions. In addition, tumour cell adhesion to endothelial cells and their invasiveness was increased after exposure to HGF/SF, and can be blocked by the presence of anti-CD44 antibodies. It is concluded that CD44 and ezrin interact in endothelial cells and that they co-localise in the areas of tumour-endothelial contact. The CD44/ezrin complex plays a pivotal role in the capture and invasion of endothelial cells by prostate cancer cells.
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PMID:Distribution and expression of CD44 isoforms and Ezrin during prostate cancer-endothelium interaction. 1237 Jul 38

Several studies suggest that cellular adhesion molecules (CAM) play a role in cancer progression and metastasis. To evaluate the role of these molecules as possible tumor markers in patients with urological malignancies, we examined the serum levels of intercellular cell adhesion molecule-1 (ICAM-1), vascular cellcular adhesion molecule-1 (VCAM-1) and E-selectin in patients with renal cell-, bladder-, prostate- and testicular cancer. Serum levels of 237 patients with urological cancers, renal cell carcinoma (n = 47), bladder cancer (n = 81), prostate cancer (n = 87) and testicular cancer (n = 22) and a group of 41 patients with benign prostate hyperplasia (BPH) as well as a 42 healthy control persons were examined for CAMs by specific ELISA tests. Serum CAM concentrations of all tumor patients were compared with controls and within the group according to T stage, N stage, tumor grade and extent of distant metastasis. Our results demonstrate that ICAM-1 and VCAM-1 serum levels are not stage dependently elevated; in contrary, they demonstrate a wide range and are highly variable throughout the different cancer types. In renal cell cancer and in bladder cancer, there is a significant difference for ICAM-1 between controls and T3 and T4 and metastatic cancers. A similar difference was found for VCAM-1, however not for E-selectin in any tumor group. Testicular cancer and prostate cancer did not demonstrate any difference in CAM serum levels between patients with tumors and controls. In metastatic renal cell-, bladder- and prostate cancer, the serum levels of ICAM-1 and VCAM-1 showed a tendency to correlate with the extent of metastatis although no statistical difference between patients with a single metastatic lesion and patients with multiple lesions could be demonstrated. The results of this study implicate a rather limited role of cellular adhesion molecules. Despite of significant ICAM-1 or VCAM-1 serum levels in some locally advanced tumors or metastatic disease, this observation does not provide enough relevant clinical information for use as tumor markers.
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PMID:Circulating intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin in urological malignancies. 1475 78

We conducted a large-scale association study to identify genes that influence nonfamilial breast cancer risk using a collection of German cases and matched controls and >25,000 single nucleotide polymorphisms located within 16,000 genes. One of the candidate loci identified was located on chromosome 19p13.2 [odds ratio (OR) = 1.5, P = 0.001]. The effect was substantially stronger in the subset of cases with reported family history of breast cancer (OR = 3.4, P = 0.001). The finding was subsequently replicated in two independent collections (combined OR = 1.4, P < 0.001) and was also associated with predisposition to prostate cancer in an independent sample set of prostate cancer cases and matched controls (OR = 1.4, P = 0.002). High-density single nucleotide polymorphism mapping showed that the extent of association spans 20 kb and includes the intercellular adhesion molecule genes ICAM1, ICAM4, and ICAM5. Although genetic variants in ICAM5 showed the strongest association with disease status, ICAM1 is expressed at highest levels in normal and tumor breast tissue. A variant in ICAM5 was also associated with disease progression and prognosis. Because ICAMs are suitable targets for antibodies and small molecules, these findings may not only provide diagnostic and prognostic markers but also new therapeutic opportunities in breast and prostate cancer.
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PMID:Large-scale association study identifies ICAM gene region as breast and prostate cancer susceptibility locus. 1560 51

Histone deacetylase inhibitors (HDACIs) represent a promising new class of antineoplastic agents that affect proliferation, differentiation, and apoptosis in both solid and hematologic malignancies. In addition, HDACIs can alter the expression of at least one cellular adhesion molecule, the coxsackie and adenovirus receptor, in bladder cancer. Because HDACIs can increase expression of a known cellular adhesion molecule, we hypothesized that migration and/or invasion may also be affected. We evaluated this hypothesis using valproic acid (VPA), a commonly prescribed anticonvulsant recently shown to have potent HDACI activity, in the bladder cancer cell lines T24 TCC-SUP, HT1376, and RT4. Analyses of cell migration and invasion were both qualitative (fluorescent microscopy) and quantitative (static and dynamic migration/invasion assays). Our results show that acute VPA treatment (72 h) causes a dose-dependent decrease in invasion for all bladder cancer cell lines, except RT4, a noninvasive papilloma. Migration, in contrast, was not affected by VPA treatment. The inhibitory effect of VPA may be cancer type-specific, because there was no difference in invasion between treated and untreated prostate cancer cell lines LNCaP, PC3, and DU145. Furthermore, when administered chronically (34 days), VPA significantly inhibits growth of T24t tumor xenografts. Our data suggest that VPA exerts some of its antineoplastic effects by inhibiting invasion as well as tumor growth, and thus it may represent a novel adjuvant strategy for patients at high risk of recurrence and/or progression of muscle invasive bladder cancer.
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PMID:Valproic acid inhibits invasiveness in bladder cancer but not in prostate cancer cells. 1686 35

Genetic susceptibility to prostate cancer has been consistently observed by a large number of studies. Recently, several pieces of evidence obtained from epidemiological and pathological studies support that chronic inflammation in prostate tissues may play a role in prostate cancer development. Multiple genes that play critical roles in inflammatory pathways have been associated with prostate cancer risk. In this article we review the key genetic findings of the associated genes. This includes 2 genes identified through family studies, ribonuclease L (RNASEL) and macrophage scavenger receptor 1 (MSR1), as well as a number of genes suggested by case-control studies, such as macrophage inhibitory cytokine-1 (MIC-1), interleukins (IL-8, IL-10), vascular endothelial growth factor (VEGF), intercellular adhesion molecule (ICAM), and Toll-like receptors (TLR-4, TLR-1-6-10 gene cluster). Overall, recent studies seem to suggest multiple genes work together to increase prostate risk, and this is consistent with the reality that inflammation is a very complex process. Thus, future studies are expected to place an emphasis on the study of gene-gene interactions. Advances in high throughput genotyping, data mining, and algorithm development are needed in order to produce interpretable results.
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PMID:Genetic variability in inflammation pathways and prostate cancer risk. 1748 24

Prostate cancer, the most frequently diagnosed cancer in Western men, can display a high variability in term of clinical aggressiveness and prognosis and none of the available markers is able to accurately predict its clinical course. Dystroglycan (DG), a non-integrin adhesion molecule, is a complex formed by two subunits, alpha- and beta-DG, which bind to extracellular matrix molecules and cytoskeleton, respectively. DG expression is frequently reduced in human cancers and has been related to tumor grade and aggressiveness. This study investigated the role of DG in human prostate tumorigenesis and its suitability as a prognostic marker. The expression level of extracellular alpha-DG subunit was frequently reduced in human prostate cancer cell lines and primary tumors and the percentage of positive tumor cells was significantly further decreased in vivo following androgen ablation therapy (median = 1%) compared to pre-treatment samples (median = 28%). A significant relationship was observed between alpha-DG staining on the post-treatment samples and tumor recurrence. A dose- and time-dependent decrease of DG expression also occurred in human prostate cancer cells following treatment with the anti-androgen flutamide. Stable expression of an exogenous DG cDNA in the LNCaP human prostate carcinoma cell line resulted in a marked inhibition of both anchorage-dependent and independent growth and of the in vivo tumorigenicity. These findings confirm and extend previous evidence that disturbances in the function of the DG complex might contribute to the definition of the malignant behavior of prostate cancer cells and suggest that androgens might regulate DG expression in these cells.
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PMID:Dystroglycan expression is reduced during prostate tumorigenesis and is regulated by androgens in prostate cancer cells. 1751 54

During the normal turnover of prostate epithelium, stem cells in the basal cell layer produce an intermediate cell population that gives rise to fully differentiated secretory luminal cells. This process is extensively studied in relation to the development of prostate disease, in particular, to elucidate the origin and nature of prostate cancer. We previously showed that the mRNA of a poorly characterised intercellular adhesion molecule, cadherin-10, is strongly expressed in human prostate. Using anticadherin-10 antibodies, immunohistochemistry, and confocal microscopy, we have examined the pattern of cadherin-10 expression in relation to human prostate epithelial differentiation markers (E-cadherin, CD44, and cytokeratins (CK) 14, 18 and 19) in archival paraffin-embedded and fixed-frozen histopathological specimens in individual and serial sections. In non-neoplastic prostate, E-cadherin is expressed by all basal and luminal epithelial cells, while cadherin-10 is variably expressed in luminal cells where it is colocalised with E-cadherin at basolateral plasma membranes. Cadherin-10 is absent in CK14- and/or CD44-positive basal cells, but is expressed in CK18-positive luminal cells (differentiated secretory cells), a subset of CK19-positive intermediate/luminal cells, but not CK19-positive basal cells. Small foci of prostate cancer express E-cadherin, CK19 and CK18, but cadherin-10 expression is low or undetectable. These findings suggest that the expression of cadherin-10 is associated with the later stages of differentiation of luminal secretory cells, indicating a specific role in secretory cell terminal differentiation. While prostate cancer cells express secretory cell markers (eg, CK18, prostate-specific antigen) and the more generally expressed E-cadherin, their failure to express cadherin-10 further emphasises a role for this cadherin in normal prostate organisation and function.
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PMID:The intercellular adhesion molecule, cadherin-10, is a marker for human prostate luminal epithelial cells that is not expressed in prostate cancer. 1808 54

Androgen deprivation causes a reduction of blood flow in the prostate gland that precedes temporally apoptosis of the epithelium. The acute response of prostate endothelial cells to androgen deprivation suggested they represent a primary target for androgen. However, rat prostate endothelial cells were reported not to express androgen receptor (AR), and the role of the androgen axis in human prostate endothelial cell (HPEC) homeostasis was poorly characterized. In this study AR expression was detected in HPEC in vivo in clinical specimens of benign prostate and prostate cancer, and AR function as a transcription factor was demonstrated in HPEC in primary xenografts of human benign prostate tissue transplanted into severe combined immunodeficient mice by iv administration of adenoviral mouse mammary tumor virus-driven luciferase expression vector. AR expression and functionality were maintained in vitro in primary cultures of HPEC that coexpressed CD31, CD34, von Willebrand factor, intercellular adhesion molecule, vascular endothelial growth factor receptor 1, and vascular endothelial growth factor receptor 2 but did not express prostate-specific antigen. AR expression in primary cultures of HPEC isolated from surgical specimens of benign prostate was validated using RT-PCR, cDNA sequencing, immunocytochemistry, and Western blot analyses. Scatchard analyses demonstrated a single ligand-binding site for R1881 in primary cultures of HPEC, with dissociation constant of 0.25 nm, and AR-mediated transcriptional activity was demonstrated using adenoviral mouse mammary tumor virus-driven luciferase reporters. Dihydrotestosterone increased proliferation in primary cultures of HPEC in a dose-dependent manner without modulating endothelial tube formation in Matrigel (BD Biosciences, Bedford, MA). Therefore, HPECs express functional AR, and androgen plays a direct role in modulating HPEC biology.
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PMID:Androgen receptor is causally involved in the homeostasis of the human prostate endothelial cell. 1829 95


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