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 usefulness of routine clinical application of the urokinase plasminogen activator in prostate cancer was evaluated. The urokinase values of prostate cancer confined to the organ, with extraprostatic spread and with metastatic disease did not differ and showed no significant difference in comparison with benign prostatic hyperplasia. Urokinase is not a useful parameter in clinical routine.
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PMID:Prognostic value of urokinase plasminogen activator for prostatic carcinoma. 751 34

The expression and function of urokinase plasminogen activator (uPA), an extracellular protease, were examined in four established prostate cancer lines, and one uPA-transfected cell line. The cell lines exhibited variable efficiency in uPA transcription, translation and specific proteolytic activity. A statistically significant inhibition of Boyden chamber invasion by anti-uPA monoclonal antibodies was demonstrated in cell lines TSU-PR1 and PC3. This inhibition suggests a direct role for uPA in the invasion of prostate cancer. However, variable processing of uPA mRNA, protein and proteolytic activity make prediction of in vitro invasion of prostate cancer difficult. Stable transfection experiments suggest that the proteolytic cascade generated by a cell is multiform and solitary alterations in uPA may not modify the proteolytic capability for invasion.
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PMID:Urokinase plasminogen activator is necessary but not sufficient for prostate cancer cell invasion. 767 30

Elevated levels of epidermal growth factor (EGF) and epidermal growth factor receptor (EGF-R) have been demonstrated in prostate cancer cell lines and clinical specimens suggesting a role for polypeptide growth factors in prostate tumor cell growth and invasion. To more clearly define the role of EGF in prostate cancer invasion, we undertook a series of studies utilizing the PC3 prostate cancer cell line, an aggressive, hormone-independent cell line derived from a metastatic lesion. No statistical differences were noted in the growth of PC3 cells under serum-free conditions when EGF (10(-10) M-10(-8) M) or monoclonal anti-EGF-R antibody (10(-11) M-10(-8) M) were added. Utilizing the Boyden chamber microinvasion assay, EGF supplemented cells demonstrated a statistically significant augmentation in invasion (P < 0.05) when compared to control cells at each time point in the study. With increasing length of exposure to EGF, the number of concentrations that produced significant invasion increased: day 1 (10(-8) M), day 3 (10(-8), 10(-9) M), and day 5 (10(-7), 10(-8), 10(-10) M). Northern blot analysis of EGF supplemented cells revealed an increase in expression of urokinase plasminogen activator (uPA) RNA, a serine protease involved in the regulation of pericellular proteolysis and membrane degradation. Protein analysis confirmed these findings. Statistically significant inhibition of invasion by anti-uPA antibodies was demonstrated for EGF-stimulated and PC3 control cells. Our results demonstrate that certain concentrations of EGF augment invasion in the PC3 cell line. This enhancement of invasion occurs in part by an overproduction of uPA, an extracellular protease. These findings suggest that the autocrine production of EGF may potentiate tumor cell invasion.
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PMID:Effect of epidermal growth factor on prostate cancer cell line PC3 growth and invasion. 829 Mar 89

Differentiation therapy may provide an alternative for treatment of cancers that do not respond to cytotoxic chemotherapy or hormonal manipulations. This hypothesis led us to evaluate the effect of a nontoxic differentiation inducer, sodium phenylacetate (NaPA), on hormone-refractory prostate cancer, the second most common cause of cancer deaths in men. NaPA treatment of androgen-independent PC3 and DU145 prostate cell lines, like that of hormone-responsive LNCaP cultures, resulted in dose-dependent inhibition of cell proliferation. Similar treatments were not significantly inhibitory to replicating normal endothelial cells and skin fibroblasts. In addition to the selective cytostatic effect, NaPA induced reversion of the prostatic cells to a nonmalignant phenotype, evidenced by their reduced invasiveness and loss of tumorigenicity in athymic mice. Phenotypic reversion was accompanied by alterations in gene expression, including selective reduction in tumor growth factor-beta 2 mRNA levels and increased amounts of class I major histocompatibility complex HLA transcripts. Furthermore, there was a decrease in tumor-associated proteolysis mediated by urokinase plasminogen activator, a molecular marker of disease progression in humans. When tumor cells were treated with NaPA together with suramin, a drug with demonstrable activity in patients, there was complete abrogation of cell growth under conditions in which each treatment alone produced only a partial effect. The in vitro antineoplastic activity was observed with drug concentrations that have been achieved in humans with no significant toxicities, suggesting that PA, used alone or in combination with other antitumor agents, warrants evaluation in the treatment of advanced prostatic cancer.
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PMID:Selective growth arrest and phenotypic reversion of prostate cancer cells in vitro by nontoxic pharmacological concentrations of phenylacetate. 848 88

The prostate gland is the most common site of cancer in men in the United States. The biologic behavior of an individual tumor, however, varies widely, with some cancers taking a relatively indolent course and other progressing rapidly to disseminated disease. Prognostic factors that might help predict a tumor's aggressiveness and invasiveness are limited. The expression of urokinase plasminogen activator was evaluated in 36 human prostate cancer specimens. Using an immunohistochemical method with monoclonal antibody #394, 70.6% (12 of 17) of cancer specimens with extracapsular extension showed increased expression of urokinase plasminogen activator, compared with 26.6% (4 of 15) of specimens without capsular invasion. Increased expression was localized to the glandular cytoplasm, with tumor stroma yielding predominantly negative results. These findings provide additional evidence of the role of urokinase in determining the biologic behavior and metastatic potential of prostate cancer.
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PMID:Urokinase-type plasminogen activator expression in human prostate carcinomas. 868 32

Metastasis represents a hallmark of the tumor cell's escape from normal cellular behavior to acquired invasive and migratory style. Metastasis of prostate cancer (Pca) depends upon the interplay of a series of hematogenous and hematopoietic factors. We investigated the role of some of those factors implicated in the dissemination process in two separate sublines of adenocarcinoma of the prostate. Our data revealed that (1) the urokinase plasminogen activator activity was significantly higher in R3327-AT3, an aggressive metastatic tumor, as compared to R3327-G, a nonmetastatic tumor of the prostate, (2) the concentration of platelets decreased, and the platelet-aggregating activity increased significantly when the platelets were reacted with exogenous aggregating agents and tumor effusions to suggest that activation of the hemostatic system could protect tumor cells from immunosurveillance and facilitate the process of hematogenous dissemination, and (3) transferrin, which has been reported to have a growth-promoting effect on Pca, did not show any appreciable effect on tumor growth but did alter the level of in vitro adherence which possibly could lead to better attachment and increased invasive behavior of tumor cells.
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PMID:Metastatic behavior of prostatic tumor as influenced by the hematopoietic and hematogenous factors. 898 19

Tumor-associated proteases play a major role in determining the biologic behavior and aggressiveness of prostate cancer. Several authors have described the association between the increased levels of urokinase plasminogen activator in the plasma and in the malignant prostatic tissue with the metastatic potential of prostate cancer. However, the direct effect of this activity in producing fibronogenolysis in patients with prostate cancer has not been addressed. To evaluate the role of chemotherapy in reversing fibrinogenolysis in patients with prostate cancer, eight patients with hormone-refractory prostate cancer, bleeding, and laboratory evidence of primary hyperfibrinogenolysis were treated with docetaxel. The drug was given 48 hr after initiation of all supportive measures. Laboratory data, including plasminogen, alpha 2-antiplasmin, and fibrinogen, were recorded before and after treatment. Prostate-specific antigen (PSA) was measured at the time of referral and before subsequent cycles (3 weeks). Five patients had resolution of the fibrinolytic process after one cycle of treatment with docetaxel. This was demonstrated by improvement in both the laboratory parameters and the bleeding episodes. Further follow-up showed stabilization of the hematologic parameters and reduction in PSA values in these patients. Two patients died from uncontrolled bleeding despite all supportive measures. One patient did not demonstrate response to this treatment in terms of normalization of the fibrinolytic indicators or reduction in PSA. Primary fibrinogenolysis associated with metastatic prostate cancer is a serious complication. Docetaxel appears to be effective in reversing this process in some hormone-refractory patients. Although this response appears to be due to antitumor activity, a direct effect on the fibrinolytic pathway induced by the tumor cannot be excluded. Further work in this area is warranted.
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PMID:Reversion of primary hyperfibrinogenolysis in patients with hormone-refractory prostate cancer using docetaxel. 1075 87

The ability of a cell to modify the extracellular matrix is important in several pathophysiological alterations including tumorigenesis. Cell transformation is accompanied by changes in the surrounding stroma as a result of the action of specific proteases such as the urokinase plasminogen activator (uPA), which has been associated with invasive potential in many tumor types. In this study, we analyzed the release of vesicle-associated uPA by the aggressive prostatic carcinoma cell line PC3 and the implications of this release for the invasive behaviour of prostatic tumor cells. Zymography and Western blot analysis revealed the presence of vesicle-associated uPA in the high-molecular weight form. Vesicles adhered to and degraded both collagen IV and reconstituted basal membrane (Matrigel), and plasminogen enhanced the degradation in a dose-dependent manner. Addition of membrane vesicles shed by PC3 cells to cultures of the poorly invasive prostate cancer cell line LnCaP enhanced the adhesive and invasive capabilities of the latter, suggesting a mechanism involving substrate recognition and degradation. Together, these findings indicate that membrane vesicles can promote tumor invasion and point to the important role of vesicle-associated uPA in the extracellular compartment.
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PMID:Vesicle-associated urokinase plasminogen activator promotes invasion in prostate cancer cell lines. 1123 92

To understand the fundamental determinants of urokinase plasminogen activator (uPA) driven angiogenesis in cancer we studied how inhibition of uPA activity could reduce neovascularization and consequently reduce tumor size in experimental animals. Proteolytic enzymes are required to mediate tumor cell invasion to adjacent tissues and initiate the metastatic process. Many different human cancers commonly overexpress the urokinase plasminogen activator system, one of the proteolytic enzyme systems. Reduction of urokinase activity in cancer cells is evidently associated with diminished invasion and metastasis. However, it has been shown recently that inhibitors of uPA could reduce tumor size also. The mechanism of action leading to decline in tumor growth rate is not clear. Proteolysis is responsible for degradation of proteins, for invasion or metastasis, but not for the proliferate properties of the cancer cells. It is difficult to envision that diminishing the size of tumor is due to simply blocking of uPA activity of cancer cells. Instead, inhibitors of uPA may be interacting with the elements of the extracellular matrix, such the neovascular bed surrounding tumors that has been reported to contain high amounts of uPA and its receptor. Overall these data strongly suggest that inhibitors of urokinase limit cancer growth by inhibiting angiogenesis. However, it is possible also that uPA inhibitors could act on cancer cells directly or prevent angiogenesis by alternative mechanisms that are not related to uPA inhibition. Therefore, we examined if plasminogen activator inhibitor (PAI-1) could limit angiogenesis. If it does, it will provide definitive evidence of uPA/PAI-1 involvement in reduction of cancer growth. Indeed, our study demonstrates that exogenously applied 14-1b PAI-1 is a powerful inhibitor of angiogenesis in three different in vitro models and is a powerful anti-cancer agent in a SCID mice model inoculated with human LNCaP prostate cancer cells.
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PMID:Recombinant PAI-1 inhibits angiogenesis and reduces size of LNCaP prostate cancer xenografts in SCID mice. 1129 64

Expression of the urokinase plasminogen activator (uPA) and its receptor (uPAR) correlates with tumour cell invasiveness and helps to determine the prognosis of prostate and other cancers. The purpose of this study was to establish in prostate cancer, the ets family and AP-1 complex transcription factors that might activate the inducible AP-1 and AP-1/PEA3 elements of the uPA enhancer. uPA and uPAR were expressed preferentially in adenocarcinoma cells, but not the stroma of high grade prostate cancers. The ets family paralogues Fli-1 and Elf-1 were also highly expressed in adenocarcinoma cells of the majority of cancers, while Erg 1,2 and Ets-2 were expressed in a minority of cancers and Elk-1, PEA3 and PU.1 were minimally expressed. A minority of cancers expressed high levels of cytoplasmic and/or nuclear c-Jun and c-Fos transcription factors. We speculate as to the molecular basis for such expression.
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PMID:Expression of urokinase plasminogen activator and receptor in conjunction with the ets family and AP-1 complex transcription factors in high grade prostate cancers. 1133 30


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