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Query: UMLS:C0376358 (prostate cancer)
 59,338 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Many grading systems for prostatic carcinoma exist; however, none allows pathologists to predict accurately the prognosis of individual patients. The Dunning R-3327 prostatic adenocarcinoma model consist of sublines of known metastatic potential which were indistinguishable until recently. A visual grading system of cancer cell motility distinguished the metastatic potentials of Dunning sublines maintained in vitro and was validated prospectively. We used this grading system to assess the metastatic potential of cells harvested directly from in vivo Dunning tumors. We graded the motility of cells from three Dunning sublines of low (less than 10%) (G, AT1, AT2) and three sublines of high (greater than 90%) AT3, (MAT-LyLu, PAT2) metastatic potential. Cells obtained from primary tumors were studied by time lapse videomicroscopy after passages 1, 3 and 5 in vivo and in vitro. Membrane ruffling, pseudopodal extension and cellular translation were graded 0-10. Serial analysis of mean and heterogeneity (coefficient of variation) of membrane ruffling, pseudopodal extension and cellular translation demonstrated that subline motility grades were assessed adequately by a sample of 10 cells. Motility did not depend upon whether cells were maintained in vitro or in vivo; however, motility increased with successive passages in four of six sublines. In 60 cells harvested directly from the fifth in vivo passage, three sublines of low metastatic potential were distinguished from three sublines of high metastatic potential (Student's t test, p less than 0.01). Individual cells from the sublines were identified correctly as high or low metastatic in 83, 78 and 70% of cases by membrane ruffling, pseudopodal extension and cellular translation respectively, and logistic regression analysis failed to improve classification accuracy. A visual grading system of cancer cell motility described the metastatic potential of in vivo neoplasms in the Dunning model and may warrant testing in human prostatic cancer.
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PMID:Prediction of metastatic potential by cancer cell motility in the Dunning R-3327 prostatic adenocarcinoma in vivo model. 173 34

Tumor cell locomotion is an integral part of the metastatic process. We present a new autocrine motility factor (AMF) derived from the serum-free conditioned medium of the Dunning R-3327 rat prostate adenocarcinoma AT2.1 tumor cell subline AT2.1-AMF, prepared by concentration of components less than or equal to 30 kDa- in size and washed free of low-molecular-weight growth factors, stimulated motility of AT2.1 cells in modified Boyden chamber migration assays. This stimulated migration was dose-dependent, and by checkerboard analysis was both chemotactic and chemokinetic. AT2.1-AMF activity was labile to heat, acid, base, reduction, oxidation, and proteases. Lyophilization and treatment with 6M urea caused a mild decrease (less than 20%) in migration-stimulating capability. Tumor-cell specificity was demonstrated for AMF of AT2.1 and AT3.1 Dunning sublines, and the A2058 human melanoma cell lines. AT2.1 cell migration to AT2.1-AMF was inhibited by 2 hr pre-treatment with cholera toxin (0.1 microgram/ml) or forskolin (100 microM), but not altered by 2 hr pre-treatment with pertussis toxin (1.0 microgram/ml). This indicates that guanine nucleotide binding protein-mediated regulation of cAMP is involved in modulating the AT2.1 cell response to its AMF. The AT2.1-AMF belongs to a related family of tumor autocrine motility factors and represents a new model for understanding the role of tumor-cell migration in the metastatic process of human prostate cancer.
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PMID:An autocrine motility factor secreted by the Dunning R-3327 rat prostatic adenocarcinoma cell subtype AT2.1. 187 63

To study the relationship between metastatic ability, mutated H-ras expression, and genetic instability, a cloned, nonmetastatic rat prostatic cancer cell line (AT2.1) was transfected with the v-H-ras oncogene. The parental AT2.1 clone, 4 control transfectants (Neo/Only), and 9 v-H-ras transfectants (Neo/Ras) were characterized with regard to their H-ras content by using Southern, Northern, and Western blot analysis and their biological behavior in vivo. Following s.c. inoculation in syngeneic rats, all transfectants produced tumors. All 4 (Neo/Only) transfectants like the parental untransfected cell were non-metastatic. Six of 9 Neo/Ras transfectants were metastatic to the lungs and lymph nodes, while the other 3 Neo/Ras transfectants were not metastatic. There was no simple dose-response relationship between the level of v-H-ras integration, mRNA or p21 protein expression, and the development of metastatic ability by the Neo/Ras transfectants. Cytogenetic analysis demonstrated that the frequency of additional structural and/or additional numerical chromosomal changes among the Neo/Ras transfectants was significantly higher than that in the Neo/Only transfectants (P less than 0.05). Loss of chromosome 10 was observed in all of the Neo/Ras transfectants, whereas that was observed in only one of the 4 Neo/Only transfectants (P less than 0.05). There were no specific chromosomal changes, however, which were statistically correlated with the development of metastases in the Neo/Ras transfectants. These results demonstrate that development of the metastatic ability in AT2.1 cells is not a single-step reaction regulated by the level of H-ras expression alone, but rather a complex process requiring additional events. One of the additional events appears to be an increase in genetic instability and cytogenetic changes following v-H-ras transfection.
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PMID:H-ras expression, genetic instability, and acquisition of metastatic ability by rat prostatic cancer cells following v-H-ras oncogene transfection. 200 21

The development of metastatic ability by cancer cells is a multifactorial process whose temporal events are complex and poorly understood. One step in the metastatic process may involve cell motility. Previous studies reported correlations between motility and metastatic ability. Whether this correlation, seen in cancer cells maintained for long periods of time, is an epiphenomenon developing late in the growth of the cancer as a selection artifact of continuous passage, or is critically required for the acquisition of metastatic ability is unknown. To investigate the relationship between cell motility and the acquisition of metastatic ability, advantage was taken of recently developed DNA transfection methods for inducing high metastatic ability in initially low metastatic cancer cells. The Dunning AT2.1 cell line, a clonal rat prostatic cancer cell line with low metastatic ability, was transfected with a plasmid containing the neomycin resistance gene alone or in combination with the v-Harvey-ras oncogene. A series of the transfected cells was isolated by limiting dilution. After the first in vitro passage following transfection, cells were inoculated into rats to characterize their metastatic ability. The same transfectants were simultaneously studied using our visual grading system of cell motility to study the early motility changes associated with newly acquired metastatic ability. The data demonstrate increased membrane ruffling, pseudopodal extension, and cell translation (translocation) in the v-H-ras-transfected cell lines with high metastatic potential.
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PMID:Early cell motility changes associated with an increase in metastatic ability in rat prostatic cancer cells transfected with the v-Harvey-ras oncogene. 304 53

To investigate the role of oncogenes in the development of metastatic ability by prostatic cancer, the viral-Harvey-ras (v-H-ras) oncogene was introduced into the Dunning rat prostate adenocarcinoma cell line, AT2.1 by means of DNA transfection. The AT2.1 cell line is a cloned cell line that is anaplastic, rapidly growing, and has low metastatic potential; after subcutaneous (s.c.) inoculation in syngeneic rats, fewer than 10% of inoculated rats develop distant metastases. Calcium phosphate mediated DNA transfections of AT2.1 cells were performed with the v-H-ras oncogene or with control DNA. The in vitro growth rate of cloned transfectants, which contain and express the v-H-ras oncogene is similar to that of untransfected AT2.1 cells and of control transfectants. After s.c. inoculation in syngeneic rats, all transfectants produced rapidly growing tumors with similar growth rates. While control transfectants had low metastatic ability comparable to untransfected AT2.1 cells, the H-ras expressing transfectants metastasized in over 80% of inoculated rats. While the mechanism by which nonmetastatic Dunning tumor sublines spontaneously develop high metastatic ability in vivo during serial s.c. passage has not been addressed in the present studies, these studies do demonstrate that expression of an activated H-ras oncogene can reproducibly convert a tumorigenic nonmetastatic prostatic cell line to a highly metastatic state.
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PMID:Expression of a transfected v-Harvey-ras oncogene in a Dunning rat prostate adenocarcinoma and the development of high metastatic ability. 305 38

Transforming growth factor-beta 1 (TGF beta 1) is a potent modulator of cell proliferation, differentiation, angiogenesis, and the immune system. TGF beta 1 messenger RNA (mRNA) levels were much higher in several rat prostate adenocarcinomas (Dunning R3327 MATLyLu, AT2, G, HI, and H sublines) than in normal prostate. Normal prostate and the well differentiated H and HI tumors produced two TGF beta 1 mRNA transcripts, 2.4 kilobases (major) and 1.6 kilobases (minor). The poorly differentiated MATLyLu and AT2 sublines produced these plus additional TGF beta 1 mRNA transcripts that were present in the primary tumors, metastases, and cultured cell lines. TGF beta 1 mRNA levels were unchanged 2 weeks after castration. Immunohistochemical staining of TGF beta 1 protein was more prominent and more extensive in prostate cancer than in normal prostate. Only extracellular TGF beta 1 staining was detected. In normal prostate and in well differentiated tumors (H and HI), extracellular TGF beta 1 staining was located in the interacinar stroma, suggesting that it may be produced there. In contrast, in the poorly differentiated tumors (MATLyLu, AT2, and G) that contain sheets of epithelial cells, extracellular TGF beta 1 staining was present throughout the tumor, suggesting that TGF beta 1 may be made and secreted by the tumor epithelial cells. MATLyLu, AT2, and G tumor cells were cultured in vitro, and the conditioned medium was analyzed for the presence of TGF beta using a bioassay. TGF beta 1 is produced and secreted as an inactive latent precursor and must be activated to release bioactive TGF beta 1. Cells secreted about 100-500 pg TGF beta/10(6) cells.24 h and were able to activate about 50% of the total TGF beta secreted. Because TGF beta 1 mRNA and protein expression are higher in cancerous than normal tissue and because prostate cancer cells themselves can activate latent TGF beta 1 to a bioactive form, TGF beta 1 produced endogenously by prostate cancer has the potential to affect tumor behavior in vivo. Therefore, TGF beta 1 may represent a new therapeutic target in prostate cancer.
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PMID:Expression of transforming growth factor-beta 1 in prostate cancer. 795 47

Physiological effectors for mitogenic cell growth control remain to be determined for mammalian tumor cells, particularly those derived from prostatic tissue. One such effector for mitogenic Ras/MAPK signaling in fibroblasts is an intermediate-conductance, calcium-activated potassium channel (FIK). In this study patch-clamp electrophysiology was used to show that both AT2.1 and MatLyLu rat prostate cancer cell lines express high levels of a current identified as FIK, based on the following criteria: activation by elevation of intracellular calcium, voltage independence, potassium selectivity, and block by charybdotoxin (ChTX) and the Stichodactyla helianthus potassium channel neurotoxin (StK). FIK current densities in AT2.1 and MatLyLu cells were comparable to the high levels seen in fibroblasts transfected with oncogenic Ras or Raf, suggesting hyperactivity of the Ras/MAPK pathway in prostatic cancer cells. Voltage-gated sodium current was present in most MatLyLu cells but absent from AT2.1 cells, and all AT2.1 cells had voltage-gated potassium currents. Thus, FIK is the main electrophysiological feature of rat prostatic cancer cells as it is for mitogenically active fibroblasts, suggesting it may play a similar growth regulatory role in both.
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PMID:The growth regulatory fibroblast IK channel is the prominent electrophysiological feature of rat prostatic cancer cells. 1070 75

Metabolism of arachidonic acid through cyclooxygenase, lipoxygenase, or P450 epoxygenase pathways leads to the formation of various bioactive eicosanoids. In this review, we discuss alterations in expression pattern of eicosanoid-generating enzymes found during prostate tumor progression and expound upon their involvement in tumor cell proliferation, apoptosis, motility, and tumor angiogenesis. The expression of cyclooxygenase-2, 12-lipoxygenase, and 15-lipoxygenase-1 are up-regulated during prostate cancer progression. It has been demonstrated that inhibitors of cyclooxygenase-2, 5-lipoxygenase and 12-lipoxygenase cause tumor cell apoptosis, reduce tumor cell motility and invasiveness, or decrease tumor angiogenesis and growth. The eicosanoid product of 12-lipoxygenase, 12(S)-hydroeicosatetraenoic acid, is found to activate Erkl/2 kinases in LNCaP cells and PKCalpha in rat prostate AT2.1 tumor cells. Overexpression of 12-lipoxygenase and 15-lipoxygenase-1 in prostate cancer cells stimulate prostate tumor angiogenesis and growth, suggesting a facilitative role for 12-lipoxygenase and 15-lipoxygenase-1 in prostate tumor progression. The expression of 15-lipoxygenase-2 is found frequently to be lost during the initiation and progression of prostate tumors. 15(S)-hydroxyeicosatetraenoic acid, the product of 15-lipoxygenase-2, inhibits proliferation and causes apoptosis in human prostate cancer cells, suggesting an inhibitory role for 15-lipoxygenase-2 in prostate tumor progression. The regulation of prostate cancer progression by eicosanoids, in either positive or negative ways, provides an exciting possibility for management of this disease.
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PMID:Role of eicosanoids in prostate cancer progression. 1208 62

Here we present research detecting the invasive activities of metastatic cells in vitro using electric cell-substrate impedance sensing (ECIS). The assay is based on previous microscopic observations, where metastatic cells added over established endothelial cell layers were observed to attach to and invade the cell layer. Human umbilical vein endothelial cells (HUVECs) werefirst grown to confluence on small gold electrodes. The impedance of these electrodes was followed after the addition of suspensions of different sublines of the Dunning murine prostatic adenocarcinoma series (G, AT1, AT2, AT3, ML, and MLL). For highly metastatic sublines, within an hour after being challenged, the impedance of the confluent HUVEC layer was substantially reduced. The effect of the weakly metastatic sublines was less pronounced, and the extent and the rate of this drop in impedance could be correlated with the metastatic potential of each of six sublines tested. The real-time assay is effective in both normal and low (1%) serum concentrations, and the detected activity requires the presence of viable transformed cells. In addition to the murine cell lines, similar behavior was observed using four established human prostatic cancer lines (DU145, PC3, TSU, and PPC1). These results suggest that this ECIS-based assay might be used with primary human cultures to establish the metastatic abilities of cells isolated from biopsies.
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PMID:Real-time impedance assay to follow the invasive activities of metastatic cells in culture. 1239 93

High spectral and spatial resolution (HiSS) MRI of rodent tumors has previously been performed using conventional spectroscopic imaging to obtain images with improved contrast and anatomic detail. The work described here evaluates the use of much faster echo-planar spectroscopic imaging (EPSI) to acquire HiSS data from rodent tumor models of prostate cancer. A high-resolution EPSI pulse sequence was implemented on a 4.7 T Bruker scanner. Three-dimensional EPSI data were Fourier-transformed along the k-space and temporal (free-induction decay) axes to produce detailed water and fat spectra associated with each small image voxel. The data were used to generate images of spectral parameters, e.g. peak-height images for each small voxel. Two variants of EPSI were performed; gradient-echo or spin-echo excitation with EPSI readout. These imaging methods were tested in commonly used rodent prostate cancers, including seven mice implanted with non-metastatic AT2.1 (n=3) and metastatic AT3.1 (n=4) prostate tumors on the hind leg, and 10 mice implanted with LNCaP prostate cancers in situ. The peak-height images derived from EPSI datasets provide more detailed tumor anatomy, improved signal-to-noise and contrast-to-noise ratios compared with the gradient-echo or spin-echo images at all echo times. The results suggest that HiSS MRI data from small animal models of prostate cancer can be acquired using EPSI, and that this approach improves imaging of heterogeneous tissue and vascular environments inside the tumors compared with conventional MR techniques.
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PMID:Comparison of high-resolution echo-planar spectroscopic imaging with conventional MR imaging of prostate tumors in mice. 1597 57


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