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Query: UMLS:C0027627 (metastases)
 103,950 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There are important interactions between prostatic tumours and bone. This study was designed to examine whether prostatic tissue can express bone inductive factors, in particular, the Bone Morphogenetic Proteins (BMPs). The polymerase chain reaction (PCR) has been used to screen for the expression of BMPs one to six in the prostatic tissue of patients with benign prostatic hyperplasia (BPH), non-metastatic prostatic adenocarcinoma and metastatic prostatic adenocarcinoma. BMPs were expressed in both benign and malignant prostate tissue and in the prostate tumour cell lines, PC3 and DU145. BMPs were also expressed in ocular melanoma tissue, a tissue which rarely metastasizes to bone. BMP-6 expression was detected in the prostate tissue of over 50% of patients with clinically defined metastatic prostate adenocarcinoma, but was not detected in non-metastatic or benign prostate samples or in ocular melanoma tissue. These findings suggest that the BMPs may play a role in the osteoinductive activity of prostate metastases and that the pattern of expression of BMPs may be important in the pathogenesis of osteoblastic metastases associated with prostate adenocarcinoma.
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PMID:Expression of bone morphogenetic proteins in human prostatic adenocarcinoma and benign prostatic hyperplasia. 128 Sep 91

In the present study, we assessed various tissue culture conditions on the motility and invasiveness of benign and malignant prostatic epithelial cells using the Boyden chamber system. In DME and RPMI-1640 media, benign human prostatic epithelial cells were unable to penetrate through a basement-membrane-coated filter. However, the prostatic carcinoma cell lines, PC3 and DU145, showed a significant frequency of invasion under those conditions. When cultured in the low-calcium WAJC 404 medium, benign prostatic epithelial cells efficiently penetrated through the basement-membrane-coated filter. PC3 and DU145 cells showed an attenuated capability to invade when cultured in WAJC 404 medium. The effect of extracellular calcium on the behavior of these cells in the Boyden chamber was further evaluated by gradual addition of calcium chloride in WAJC 404 medium. These studies showed that the number of benign prostatic epithelial cells penetrating through the filter decreased as the calcium ion concentration increased. Conversely, the number of PC3 cells invading through the filter increased as calcium ion concentration was increased to 0.4 mM and decreased at higher calcium ion concentrations. These results suggest that the extracellular calcium concentration is one of the factors which may affect cell behavior in the Boyden chamber system.
Invasion Metastasis 1992
PMID:Utilization of the Boyden chamber to further characterize in vitro migration and invasion of benign and malignant human prostatic epithelial cells. 128 46

Prostatic cancer typically produces osteoblastic metastases which are not attended by marrow fibrosis (i.e., osteoblast but not stromal fibroblast proliferation). In the present study we sought to test the hypothesis that prostatic cancer cells produce factor(s) which act selectively on human osteoblasts. Such a paracrine mechanism would explain the observed increase in osteoblasts, unaccompanied by an increase in marrow fibroblasts. To test this hypothesis we investigated the mitogenic activity released by the human prostatic tumor cell line, PC3. PC3 cells have been reported previously to produce mitogenic activity for cells that was relatively specific for rat osteoblasts compared to rat fibroblasts. However, the effects of this activity on human cells has not been examined previously. PC3-conditioned medium (CM) (5-50 micrograms CM protein/ml) stimulated human osteoblast proliferation by 200-950% yet did not stimulate human fibroblast proliferation [( 3H]thymidine incorporation). PC3 CM also increased cell numbers in human osteoblast but not fibroblast cell cultures. To determine whether the osteoblast-specific mitogenic activity could be attributed to known bone growth factors, specific assays for these growth factors were performed. PC3 CM contained 10 pg insulin-like growth factor (IGF) I, less than 2 pg IGF II, 54 pg basic fibroblast growth factor, and 16 pg transforming growth factor beta/microgram CM protein. None of these growth factors alone or in combination could account for the observed osteoblast-specific PC3 cell-derived mitogenic activity. Furthermore, when 5 micrograms/ml PC3 CM was tested in combination with maximally effective concentrations of either basic fibroblast growth factor, IGF I, IGF II, or transforming growth factor beta, it produced an additive effect suggesting that PC3 CM stimulates osteoblast proliferation by a mechanism independent of these bone mitogens. Biochemical characterization supported the hypothesis that the PC3 cell growth factor was unique from other growth factors. The PC3 growth factor did not bind to heparin and was resistant to acid as well as the reducing agent, dithiothreitol. Sephadex G-75 and fast protein liquid chromatography Mono S cation-exchange chromatography revealed the PC3-derived mitogen to be an Mr 26,000-30,000 basic protein. Therefore, we conclude that PC3 cells release a mitogen which exhibits higher specificity for human osteoblasts than human fibroblasts and is unique from other growth factors tested. Production of this mitogen by human prostatic carcinoma cells could play an etiological role in the intense osteoblast-specific stimulation that occurs at sites of bone metastases.
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PMID:Human prostatic cancer cells, PC3, elaborate mitogenic activity which selectively stimulates human bone cells. 169 44

To increase our understanding of the potential role of basic fibroblast growth factor (bFGF) in malignant progression of prostate cancer, we determined the production of bFGF, the expression of FGF receptor (flg), and the response to exogenous bFGF in LNCaP, DU 145, and PC 3 cells. We observed that these three prostate cancer cell lines, which differed in their dependence on androgens for growth in vitro and in their in vivo behavior in nude mice, could be distinguished as follows: (a) androgen-sensitive LNCaP cells, which do not metastasize in nude mice, did not produce measurable amounts of bFGF, expressed small but measurable amounts of FGF receptor mRNA, and did respond to exogeneous bFGF; (b) androgen-insensitive, moderately metastatic DU 145 cells did produce measurable amounts of biologically active bFGF, expressed large amounts of FGF receptor mRNA, and responded to exogeneous bFGF and the heparin-binding fractions from DU 145 cell extracts; (c) androgen-insensitive and highly metastatic PC3 cells also produced measurable amounts of bFGF but did not demonstrate a growth response to either the heparin-binding fractions from PC3 cell extracts or exogenous bFGF, even though large amounts of FGF receptor mRNA were expressed in PC 3 cells. These results suggest the possibility that differences in production of, and response to, bFGF may be associated with different biological behavior.
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PMID:Basic fibroblast growth factor in human prostate cancer cells. 173 45

Transforming growth factor beta (TGF beta) exerts a wide spectrum of activity on many different cell types. Since TGF beta inhibits the growth of a variety of epithelial tumor cells in vitro, we examined the effects of TGF beta on the human prostate cancer cell lines DU145, PC3 and LNCaP for possible inhibitory activity. Growth in monolayer was initially inhibited in a dose-response fashion in the two androgen-independent cell lines, PC3 and DU145 but not in the androgen-dependent LNCaP cells. The rate of growth of the PC3 and DU145 cells treated with TGF beta, however, eventually returned to control levels despite retreatment with TGF beta. Anchorage-independent growth was inhibited to 55% and 16% control levels in PC3 and DU145, respectively. Scatchard analysis showed 1500 and 2900 TGF beta binding sites/cell on DU145 and PC3 cells with Kd = 6.9 and 12 x 10(-12) M, respectively. High-affinity binding could not be demonstrated on LNCaP cells. We also explored the possibility that TGF beta was secreted by these cells. Analysis of conditioned media by immunoprecipitation and a radioreceptor assay showed secretion of TGF beta into the media by DU145 and PC3 but not by LNCaP. Northern analysis showed the presence of TGF beta mRNA in DU145 and PC3, but not in LNCaP. These data indicate that TGF beta might serve as an autocrine inhibitory factor in prostate cancer. In addition, because TGF beta affects a wide range of cell types, TGF beta production by prostate cancer cells may contribute an important paracrine function in the development of tumor stromal tissue and metastases.
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PMID:Differential effects of transforming growth factor beta on human prostate cancer cells in vitro. 254 87

This report characterizes a prostate-specific monoclonal antibody, KP-P8, which was prepared against the human prostate cell line PC3. The antigen detected by KR-P8 was identified on the surfaces of 90% of cells of the PC3 line, as well as on 67% of cells of the Du-145 prostate line, but it was absent from the surfaces of normal peripheral blood leukocytes and cells of a number of lymphoblastoid lines. As judged by immunoperoxidase staining techniques, KR-P8 reacted with the glandular epithelium of all specimens of normal, benign hypertrophic, and malignant prostate glands tested. However, no reactivity was noted with numerous other human tissues including normal bladder, lung, liver, kidney, testis, colon, parotid gland, thyroid gland, and spleen. These results indicate that the antigen detected by KR-P8 is prostate organ-specific. Competitive blocking studies showed that the antibody did not recognize the previously described prostate-specific antigen or the alpha-Pro-3 antigen described by other investigators. The KR-P8 antibody also did not bind to purified prostatic acid phosphatase. The presence of the KR-P8 antigen was demonstrated in cell-free preparations of dilute seminal plasma by radioimmunoassay, indicating that this antigen is secreted by the glandular cells of the prostate gland. The clinical significance of this marker was demonstrated by its ability to identify prostate metastases of the lymph node.
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PMID:Characterization of a monoclonal antibody, KR-P8, that detects a new prostate-specific marker. 620 70

Expression of CD44, the cellular hyaluronate receptor, was examined in human prostate cell lines. CD44 mRNA was detected in cell lines PC3 and DU145, both established from organ metastases of prostate adenocarcinoma, but not in cell line LNCaP, established from a lymph node metastasis. PC3 and DU145, but not LNCaP, are tumorigenic and metastatic in nude mice. Of the CD44 mRNA species identified, the standard CD44s as well as variant isoforms CD44v7, CD44v10, CD44v14, CD44v13-v14, CD44v12-v14 and CD44v7-v14 are represented.
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PMID:Expression of CD44 in prostate cancer cells. 751 Feb 14

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.
Invasion Metastasis 1995
PMID:Urokinase plasminogen activator is necessary but not sufficient for prostate cancer cell invasion. 767 30

Highly invasive cell subpopulations from a human prostate carcinoma cell line, PC-3, were selected for by allowing the parental PC-3 cells to invade through reconstituted basement membrane, Matrigel. These cells were collected, cultured and then selected further by repeated invasion through the in vitro invasion chamber. The invasive subpopulations (I-PC3 (2) and (3)) were found to be approximately 15-fold more invasive in vitro than the parental cells, had a distinct rounded morphology in culture, and proliferated more rapidly than the parental cells. When injected either subcutaneously or intraperitoneally into immunocompromised SCID mice, the I-PC3 cells were found to form tumors at the primary sites and to be highly invasive and metastatic. In contrast, the parental PC-3 cells formed tumors at the site of inoculation in these mice but failed to invade or metastasize. The I-PC3 cells attached equally as well as PC-3 cells to fibronectin, laminin, collagen type IV and vitronectin, but unlike the parental PC-3 cells these invasive variants failed to spread on any of these substrates. On Matrigel, the PC-3 cells became highly organized, whereas the I-PC3 cells remained rounded, clumped together and penetrated into the Matrigel. Biochemical analysis of the expression of adhesion proteins and integrins demonstrated that whereas the parental cells synthesized and secreted substantial amounts of fibronectin, the I-PC3 cell variants did not secrete any fibronectin. Although both PC-3 and I-PC3 cells expressed equivalent levels of cell surface alpha v beta 3, alpha 2 beta 1 and alpha 5 beta 1 integrins, the expression of the alpha 3 beta 1 integrin, which is expressed at very high levels on the parental PC-3 cells, was drastically reduced on the invasive I-PC3 cells. This decrease in expression of alpha 3 occurred also at the level of mRNA expression. Finally, whereas the PC-3 cells express alpha 6 beta 1, in the invasive I-PC3 cells the alpha 6 subunit was associated mostly with the beta 4 subunit. Since the alpha 6 beta 4 integrin is analogous to the A9 tumor antigen which is associated with aggressive human squamous cell carcinomas, the apparent overexpression of alpha 6 beta 4 may also participate in the aggressive behavior of these variant prostate carcinoma cells. Alterations in the expression of the alpha 3 beta 1 and alpha 6 beta 4 integrins may thus allow these cells to become more invasive, and lead to an increased propensity for metastasis.
Clin Exp Metastasis 1993 Sep
PMID:Specific alterations in the expression of alpha 3 beta 1 and alpha 6 beta 4 integrins in highly invasive and metastatic variants of human prostate carcinoma cells selected by in vitro invasion through reconstituted basement membrane. 837 14

The plasminogen activator urokinase (u-PA) mediates proteolysis by a variety of human tumor cells. Competitive displacement of u-PA from cellular binding sites results in decreased proteolysis in vitro, suggesting that the cell surface is the preferred site for u-PA-mediated protein degradation. We studied the effect of u-PA receptor blockade on the metastatic capacity of human PC3 prostate carcinoma cells, using transfectants which expressed chloramphenicol acetyl-transferase (CAT). Eight weeks after subcutaneous inoculation of these cells into nude mice, CAT activity was detected in regional lymph nodes, femurs, lungs, and brain, thereby mimicking the organ tropism observed for naturally occurring metastases of prostate cancer. In a second transfection, CAT-expressing PC3 cells received cDNA encoding a mutant u-PA (Ser356-->Ala) which lacks enzymatic activity but which retains full receptor binding affinity. Three mutant u-PA expressors, each with < 5% of wild-type cell-associated u-PA activity, were compared in vivo with independently derived controls. Primary tumor growth was similar in each group of animals and all tumors expressed comparable CAT activity. In contrast, metastasis (as assessed by CAT activity) was markedly inhibited when cell surface u-PA activity was blocked. Levels of CAT activity were reduced by a factor of > 300 in regional lymph nodes, 40-100 in brain tissue, and 10-20 in lung tissue. Metastatic capacity was inhibited similarly when animals were given intermittent intraperitoneal injections of a u-PA/IgG fusion protein capable of displacing u-PA activity from the tumor cell surface. Our results indicate that cell surface u-PA activity is essential to the metastatic process. In addition, the assay system employed in these experiments may be generally useful in testing other therapeutic modalities to limit the spread of primary tumors.
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PMID:Prevention of metastasis by inhibition of the urokinase receptor. 838 64


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