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

A human prostate cancer model was established by inoculating a prostate specific antigen (PSA)-producing LNCaP cell line with either prostate or bone fibroblasts. Alternatively, this human prostate cancer model can also be established by inoculating LNCaP cells with growth factor(s) (GFs) and extracellular matrix (ECM) immobilized on Gelfoam. The resulting LNCaP tumors were used to evaluate PSA production and excretion in athymic hosts. This model was also employed to examine the biochemical nature of mesenchymal cell-derived growth-promoting protein(s) and to assess the efficacy of potential chemotherapeutic agents. Because of the propensity of human prostate cancer to metastasize to the bone, this study defined a 1.0 M NaCl-eluted fraction, MS1, from the conditioned medium of a bone stromal cell line (MS) by heparin-affinity column chromatography. The growth-promoting activity was assayed both in vivo (e.g., tumor formation) and in vitro (e.g., soft agar colony formation). We found that the growth-promoting activity was trypsin- and heat-sensitive, and partially degraded by acid and dithiothreitol. Immunochemical studies indicated that the polyclonal antibody raised against MS1 blocked the growth-promoting effect elicited by the bone-conditioned media. This growth-promoting factor was found to be immunochemically dissimilar to KGF, HGF, and bFGF. However, addition of bFGF, HGF and NGF, but not aFGF, TGF beta, IGF1, IGF2, PDGF, EGF, TGF alpha and KGF, stimulated anchorage-independent growth of prostate cells, a condition closely parallel to tumor formation in vivo. We found that the MS1 fraction also contained fibronectin and tenascin but not laminin or collagen IV.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Human prostate cancer model: roles of growth factors and extracellular matrices. 128 80

Prostate cancer selectively metastasizes to the axial skeleton to produce osteoblastic lesions, which suggests that bidirectional paracrine interactions exist between prostate cancer and bone cells. To evaluate the role of tumor-stromal cell interaction and stromal-specific growth factors in prostate cancer growth and dissemination, we coinoculated nontumorigenic human prostate cancer cells (LNCaP) and various tissue-specific fibroblasts subcutaneously in athymic mice. LNCaP tumors were induced most consistently by human bone fibroblasts (62%), followed by two prostate fibroblast cell lines (31% and 17%), but not by lung, kidney, or embryonic 3T3 fibroblasts. Carcinomas formed preferentially in male hosts, demonstrating in vivo androgen sensitivity. Immunohistochemical and biochemical techniques confirmed the human prostate component of these tumors and were paralleled by elevations in serum prostate specific antigen. In vitro mitogenic assays revealed a two-to three-fold bidirectional stimulation between LNCaP and bone or prostate fibroblast conditioned media, but not lung, kidney, or 3T3 fibroblast conditioned media. A novel method developed to deliver concentrated bone or prostate fibroblast conditioned media in vivo using a slowly absorbed matrix (gelfoam) also induced tumor formation, emphasizing the importance of fibroblast growth factors in LNCaP tumor formation. Northern analysis identified the stromal compartment as the primary source of extracellular matrix (collagen, fibronectin), while only LNCaP cells expressed transforming growth factor alpha. Although LNCaP and stromal cells express basic fibroblast growth factor (bFGF), the bidirectional paracrine-mediated mitogenic activity between these cells is not inhibited by anti-bFGF antibodies, suggesting that other undefined growth factors may be involved in stimulating LNCaP growth. These observations illustrate the importance of stromal-epithelial interaction in prostate tumor growth and suggest that extracellular matrix and paracrine-mediated growth factors play a role in prostate cancer growth and metastasis.
 ...
PMID:Prostate and bone fibroblasts induce human prostate cancer growth in vivo: implications for bidirectional tumor-stromal cell interaction in prostate carcinoma growth and metastasis. 137 62

Cell density, nutritional state, and serum factors modify the growth response of LNCaP human prostatic cancer cells to dihydrotestosterone. Evaluation of growth response to dihydrotestosterone requires logarithmic transformation of cell count or thymidine incorporation data. Under conditions of dose response, growth increases with cell density but no significant interaction of dihydrotestosterone with cell density was found under optimal culture conditions. The frequency of media change was a significant factor in modulating dose response. When cells from cultures maintained at different feeding periods were plated at different cell densities of (trypan blue) viable cells, significant effects of plating density on dihydrotestosterone response were found. Dihydrotestosterone protects cells under the adverse effects of media deprivation. Under the extreme adverse effects of serum deprivation, cells respond to dihydrotestosterone even under conditions of increasing cell loss. The effects of dihydrotestosterone on final cell density were significant. In the absence of serum, the elongated cells of LNCaP assume a round shape, but many remain adherent to the culture dish and can be restored to normal morphology by serum. A number of growth factors fail to restore normal morphology that was completely restored by a combination of fibronectin and dihydrotestosterone. We have not developed a practicable serum-free system for LNCaP.
 ...
PMID:The effect of dihydrotestosterone and culture conditions on proliferation of the human prostatic cancer cell line LNCaP. 144 Jun 97

Monoclonal antibodies to human prostate adenocarcinoma membrane antigens were produced by fusion of P3X63/Ag8 mouse myeloma cells with spleen cells from BALB/c mice immunized against the prostate cancer cell line DU145. The hybrids were screened for antibody production using glutaraldehyde-fixed cells in a solid-phase radioimmunoassay. Antibody-binding specificity was also checked by quantitative adsorption, membrane immunofluorescence, and complement-dependent cytotoxicity assays. A hybridoma clone (83.21) was isolated that secreted antibodies which preferentially bound to several prostate and bladder cancer cell lines but did not bind to a variety of other normal and malignant human cell lines. This antibody also reacted with a cytomegalovirus-transformed human embryonic lung cell line but not to normal human embryonic lung cells. Quantitative adsorption studies demonstrated that the 83.21 monoclonal antibody was strongly reactive to membrane preparations from human prostate adenocarcinoma tissue and a liver metastasis of prostate carcinoma. Little or no binding activity was observed against two other prostate carcinomas, bening prostatic hyperplasia, normal prostate, or normal liver. Binding studies indicate that the 83.21 monoclonal antibody does not bind to alpha-fetoprotein, carcinoembryonic antigen, prostatic acid phosphatase, human leukocyte antigen, beta 2-microglobulin, HLA-Dr antigens, fibronectin, or prostate antigen. The data indicate that we have isolated a monoclonal antibody that binds to an antigen(s) expressed by several urogenital carcinoma cell lines as well as human prostate tumor tissue and that the antibody is not directed against well-known human tumor cell markers.
 ...
PMID:Monoclonal antibodies to human prostate and bladder tumor-associated antigens. 704 15

The levels of fibronectin in urine from patients with prostatic cancer, from patients with benign urologic disease, and from healthy control individuals were determined by the use of a gelatin affinity chromatography procedure. The assay does not seem to give false positive results, inasmuch as evaluation of 16 patients with benign urologic disease showed urinary fibronectin levels in the same range as those found in healthy controls. For a single determination, the levels in 42 per cent of prostatic cancer patients were elevated above control levels; when prostatic cancer patients were evaluated sequentially, the determination of urinary fibronectin levels over three sampling times approached a 100 per cent correlation with presence of disease. Inasmuch as levels of urinary fibronectin episodically elevate in patients with prostatic carcinoma, the differential frequency and magnitude of urinary fibronectin elevations may be useful markers to assess tumor aggressiveness and to monitor the impact of a therapeutic modality.
 ...
PMID:Urinary fibronectin: potential as a biomarker in prostatic cancer. 735 3

The cysteine endopeptidase cathepsin B (CB) can degrade basement membrane (BM) proteins (such as laminin, type IV collagen, and fibronectin) at both acid and neutral pHs suggesting that CB has a role in tumor invasion and distant metastasis. The distribution and intensity of CB protein localization vary in normal prostate, benign prostatic hyperplasia (BPH), and neoplastic prostate. These considerations have led us to examine whether the distribution of CB localization in malignant and normal cells is due to storage or active synthesis of CB. In the present study, we examined the localization patterns of CB at the mRNA level in normal prostate, BPH, and well to moderately differentiated neoplastic prostate, focusing on invasive groups of cells and invasive edges of malignant tumors. We used a 25-base biotinylated oligonucleotide CB cDNA "sense" probe to localize CB message in prostate samples obtained from radical prostatectomies. We have determined that CB is actively synthesized by the epithelia of normal, hyperplastic, and neoplastic prostate including some invasive cells in the invasive edges. In both normal and BPH, CB mRNA was localized predominantly in acinar basal cells with some localization in cuboidal/columnar cells. In contrast, in neoplastic prostate, CB mRNA was localized predominantly in columnar cells and in groups of invasive cells and invasive edges. Thus, in malignant prostate the predominant cell types expressing CB differed from those of the normal prostate and BPH. Analysis of CB mRNA localizations indicated a heterogeneity in staining distribution in prostate cancer with some invasive groups of cells and invasive edges exhibiting CB mRNA and others exhibiting little or no reaction products.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Localization of a biotinylated cathepsin B oligonucleotide probe in human prostate including invasive cells and invasive edges by in situ hybridization. 767 71

In this study, tissue fibronectin levels have been assayed in human prostatic cancer, benign prostatic hyperplasia and normal prostatic tissue. The mean tissue fibronectin levels for prostatic cancer, benign prostatic hyperplasia and normal groups were found to be 20.22 +/- 8.66 micrograms/mg protein and 11.77 +/- 6.74 micrograms/mg protein, respectively. In the malignant group, the mean fibronectin concentrations, appeared to be significantly higher than normal, (p < 0.05). On the other hand, fibronectin levels of benign prostatic hyperplasia were found to be statistically insignificant in comparison to the normal group (p > 0.05).
 ...
PMID:Tissue fibronectin levels of human prostatic cancer, as a tumor marker. 859 Apr 35

We investigated the tissue concentration of sialic acid and fibronectin in patients with prostatic cancer. The mean sialic acid and fibronectin levels in patients with prostatic cancer were 19.02 +/- 6.30 micrograms/mg protein, respectively versus 13.01 +/- 4.53 micrograms/mg protein and 11.77 +/- 6.74 micrograms/mg protein for normal prostatic tissues. Sialic acid and fibronectin levels in cancerous patients were significantly higher than in the control group (P < 0.05).
 ...
PMID:Tissue sialic acid and fibronectin levels in human prostatic cancer. 861 16

Since its identification in seminal fluid in 1971, much new information has been obtained about the biology and expression of prostate-specific antigen (PSA). PSA is a glycoprotein composed of 93% amino acids and 7% carbohydrates, with a molecular weight of about 30,000 Da. Functionally and structurally PSA is a kallikrein-like serine protease, and its physiologic role is degradation of the major proteins of seminal coagulum (semenogelin I and II, fibronectin), which leads to semen liquefaction. The PSA gene is located on the 13q region of chromosome 19, and it has a high degree of homology (more than 80%) with genes of the human glandular kallikrein (hKGK1). PSA production and expression are preferentially but not exclusively associated to the normal, benign hyperplastic and cancerous tissues of the prostate. In fact, it has been demonstrated that PSA is also present in accessory male sex glands and breast cancer. It was recently reported that PSA was also present in milk of lactating women. Many factors may influence PSA synthesis and production, and among them the most important are androgen, retinoic acid and growth factor stimulation. Significant advances have been recently made as regards the molecular isoforms of PSA. In the seminal fluid PSA seems partially bound to a serpine (protein C inhibitor), whereas in serum it is predominantly associated to alpha-1-antichymotrypsin and in a small quantity to alpha-2-macroglobulin. These new findings will have implications for the clinical application of PSA as a tumor marker for prostate cancer.
 ...
PMID:Biochemical characteristics and recent biological knowledge on prostate-specific antigen. 862 11

Development and progression of prostate cancer is a multistep process of cumulative genetic damage, acquired during a life-time. However, the altered genotype acts against an appropriate background of epigenetic control mechanisms. Several mechanisms of mitotically heritable, epigenetic control of differential gene transcription have been noted, such as stromal-epithelial and cell-cell interactions. In prostate cancer, an important, supporting and/or inhibiting role of stromal-epithelial interaction has been implicated in tumor growth, angiogenesis and metastasis, which includes cell proliferation, adhesion and motility. Within these processes, data mainly obtained in systems other than the prostate have shown a crucial (regulatory) role of proteoglycans (PGs) acting at the level of cell-cell and cell-pericellular matrix interactions. Although little information has been recorded from normal, benign hyperplastic and malignant prostate tissue, PGs are components of both the cell surface and the extracellular matrix (ECM) that form associations with other molecules, such as fibronectin and laminin. On the basis of cell-ECM adhesion/interaction as a prerequisite for both cell proliferation and motility, and the involvement of PGs, the purpose of this study was to investigate the possible biological relevance of (free) glycosaminoglycans (GAGs), as major functional substructures of PGs, on cell adhesion of a series of human prostatic cell lines cultured in vitro. The effects of a series of exogenously applied GAGs on cell adhesion and proliferation were studied in the human cell lines LNCaP, DU 145 and PC-3, cultured on tissue culture plastic as substratum. The applied GAGs were the natural GAGs heparin, heparan, dermatan, chondroitin-4 and chondroitin-6 sulfate, and the semisynthetic, GAG-like pentosan polysulfate (PPS). Addition of GAGs (1-300 micrograms/ml) to cultures that were allowed to adhere for 24 h prior to GAG addition did not affect cell proliferation. In contrast, whereas the natural GAG added during cell adhesion had no effect. PPS strongly inhibited proliferation of LNCaP and DU145, but not the less anchorage-dependent PC-3 cells. Under the latter conditions, after 6 days of culturing the IC50 of proliferation were determined to be < 1 and 50 micrograms PPS/ml for LNCaP and DU145, respectively, corresponding with a profound effect on cell morphology. Direct measurements of cell adhesion confirmed that, in contrast to the natural GAGs, PPS inhibited cell adhesion. In conclusion, the interference of a nonnatural, GAG-like structure with cell adhesion may be interpreted as the involvement of PGs of the cell surface in cell adhesion, possibly affecting the various processes (proliferation, angiogenesis and metastasis) of prostate tumor progression. Although similar interferences of nonnatural GAGs with cell-adhesion-associated proliferation of anchorage-dependent cells remain to be established under in vivo conditions, this type of compounds deserves further attention as a tool with which to study the role of cell adhesion in the progression of prostate cancer and as a potential candidate for the development of a stromal-epithelial targeted therapy.
 ...
PMID:Role of proteoglycans in cell adhesion of prostate cancer cells: from review to experiment. 914 93


1 2 3 4 5 6 7 8 9 10 Next >>