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

Using monolayer cultures of clonally isolated C3 and T5 rat prostate cancer cells, we determined that acidic (aFGF) and basic (bFGF) fibroblast growth factors profoundly enhanced T5 cell thymidine incorporation with half-maximum stimulation at 0.53 and 0.35 ng/ml, respectively. In contrast, aFGF or bFGF enhancement of C3 cell thymidine incorporation was about 5% of that of T5 cells, and effects were principally mitogen concentration independent. Saturation analyses and cross-linking studies established that both C3 and T5 cells contained high-affinity FGF receptors of 120 and 145 kilodaltons and that receptor content and Kd of C3 and T5 cells were comparable. aFGF or bFGF stimulation of T5 cell thymidine incorporation profoundly decreased as cell plating density was reduced from 1.5 x 10(5) to 1.0 x 10(4) cells/well. The modest response of C3 cells to either aFGF or bFGF also decreased as cell plating density was reduced. Because heparin preserves FGF biological activity and enhances bFGF binding to high-affinity FGF receptors, we examined the effect of heparin on FGF stimulation of C3 cell thymidine incorporation. We found that changes in cell plating density and/or medium heparin concentration had variable, inconsistent effects. These were C3 cell plating density associated and included inhibition or modest enhancement of FGF effects. Binding analyses established that high-affinity bFGF binding of C3 and T5 cells immediately prior to assessing FGF-stimulated thymidine incorporation was comparable and independent of cell plating density, implying that C3 cell FGF insensitivity was not attributable to differences in C3 and T5 cell FGF receptor content at the time of mitogen stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Signal transduction defect appears to be the cause of rat prostate cancer cell fibroblast growth factor insensitivity. 144 1

We review in this paper the role of heparin-binding growth factor (HBGF*) or fibroblast growth factor (FGF*), rat prostate cancer cells produce TGF-beta, IGF-II* and OGF*. Of these growth factors, TGF-beta and unknown labile factor with 19 kDa are the most probable candidates responsible for osteoblastic bony metastasis of prostate cancer. In vitro experiments suggest that TGF-beta modulates cell detachment of prostate cancer cells together with nutritional factors. HBGF-dependent growth of the prostate tumor epithelial cells is free from inhibition by TGF-beta, whereas normal prostate epithelial cells are sensitive to TGF-beta inhibition. Transfection experiments suggest that HBGF-2 (basic FGF) might be closely related to the malignant growth of prostate cancer, in addition to tumor angiogenesis.
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PMID:Potential role of HBGF (FGF) and TGF-beta on prostate growth. 149 11

Growth of the normal and malignant prostate is known to be regulated by androgens. Part of their effect has been suggested to be mediated through coordinated regulation of secreted growth factors with autocrine function. We now examine the biological role of preferentially paracrine acting factors in growth control of prostate cancer, i.e. fibroblast growth factor(s) (FGF). Coculture experiments using the androgen-responsive human prostate carcinoma cell line LNCaP as feeder cells and the FGF-dependent human adrenal carcinoma SW-13 cell line as target cells show that (i) LNCaP cells induce growth of SW-13 cells, (ii) even higher stimulation of SW-13 cells is seen in the presence of androgen treated LNCaP cells and (iii) a specific anti-bFGF antibody inhibits growth of SW-13 cells induced by androgen treated LNCaP cells; no proliferation of SW-13 cells occurs in the absence of LNCaP cells. Partial purification of the secretory products of LNCaP cells was performed by affinity chromatography using a heparin sepharose column. Fractions were tested for biological activity in a soft agar assay with SW-13 cells. Several activities could be detected, the main activity was eluted with about 1.5 M NaCl. These data suggest that androgen treatment of LNCaP cells leads to enhanced secretion of proteins which belong to the FGF-family.
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PMID:Regulation of fibroblast growth factor-like protein(s) in the androgen-responsive human prostate carcinoma cell line LNCaP. 156 38

The growth of human prostate cancer and its relationship to the surrounding stroma are controlled by complex mechanisms that are incompletely understood. Clearly, peptide growth factors appear to have crucial roles in these processes. One of these factors, TGF-beta, and its family members are notable for their wide spectrum of biological effects. In terms of growth, TGF-beta inhibits the growth of prostate cancer cells in a cytostatic fashion while stimulating the growth of critical stromal cells, such as fibroblasts. Since the inhibitory effects of TGF-beta on prostate cancer cells appear to diminish as the process of transformation progresses towards less differentiated states, the net effect on prostate tumour growth may be positive. Recent evidence suggests that the inhibitory effects of TGF-beta on growth, at least, might be mediated through the RB tumour suppressor gene product and the proto-oncogene c-myc. Beyond its direct growth effects, TGF-beta also alters the response of prostate cancer cells to positive mitogenic factors, such as members of the EGF and FGF families, suggesting that growth control is a delicate balance between positive and negative influences. Non-mitogenic responses to TGF-beta by prostate cancer cells, the immune system, the stroma and the vascular system provide evidence that TGF-beta might also be important in the processes of carcinogenesis, tumour establishment and metastases. In addition, TGF-beta appears to influence metabolic pathways important to drug metabolism and steroidogenesis. In vivo, limited evidence suggests that TGF-beta can alter the growth and differentiation of some tumour types but appears to be very toxic when administered in high doses. A better understanding of the response of prostate cancer cells to members of the TGF-beta family may open new avenues of treating and controlling this disease.
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PMID:Response of prostate cancer cells to peptide growth factors: transforming growth factor-beta. 184 49

Extracts of human benign prostatic hyperplasia, well-differentiated prostatic adenocarcinoma, and normal post-pubertal prostate stimulate 3H-thymidine incorporation by resting phase cultures of fetal rat osteoblasts and fibroblasts. The stimulation is concentration dependent and reaches a maximum at twenty-four hours of incubation. Prostatic extracts are also mitogenic in cell cultures of newborn human foreskin fibroblasts and the human cell lines, BUD-8 and DoT. The growth-stimulating factor is both heat and trypsin sensitive indicating that the factor is either a protein or contains a protein moiety. The growth-stimulating activity is not related to prostatic polyamine concentration. Experiments also show the activity is not due to human prostatic acid phosphatase. A prostatic growth factor may explain the growth of fibrous nodules in benign prostatic hyperplasia and the osteoblastic response of bone to prostatic cancer.
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PMID:Mitogenic factor in human prostate extracts. 696 86

Previous studies have shown that part of steroid hormone action on hormone dependent carcinoma cells is mediated through secreted autocrine and paracrine growth factors. Coculture experiments using the androgen receptor positive human prostate carcinoma cell line LNCaP as feeder cells and the androgen receptor negative prostate cell line DU 145 as indicator cells, such as experiments with conditioned medium suggest that androgens might regulate proliferation of prostate carcinoma through a similar mechanism. LNCaP and DU 145 cells express high affinity EGF-receptors and show an increased growth rate under treatment with EGF, TGF alpha and FGF. The growth stimulating potential of LNCaP-conditioned medium can be enhanced by androgens. The polyanionic compounds suramin and dextran sulfates which have been shown to inactivate a variety of growth factors e.g. EGF/TGF alpha inhibit growth of LNCaP cells and DU 145 cells in a dose dependent and reversible fashion. Growth stimulation of LNCaP cells by EGF/TGF alpha can be completely reversed by simultaneous addition of polyanions but they inhibit androgen stimulation only partially. These data suggest the existence of at least two different mechanisms of growth regulation by androgens which can be distinguished by their different sensitivity of prostatic carcinoma cells to growth factor inhibitory agents. In order to investigate the therapeutic potential of these substances in complex, heterogeneous cell systems of solid tumors we treated 8 representative human prostate cancer lines in the nude mouse model. Systemic applications of polyanions revealed significant growth inhibition in hormone dependent as well as hormone independent xenografts. In androgen responsive lines growth inhibition was intensified by additional androgen withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Androgen regulation of secreted growth factors in prostate carcinoma cell and tumor lines]. 751 Dec 69

Prostatic cancer is the second most frequent cancer in men in industrialised countries. The histological analysis of its initial development demonstrates the existence of precancerous lesions, PIN. The initial presence of several different cell populations accounts for the development of contingents of hormone-sensitive and hormone-resistant cells. The presence of numerous neuroendocrine cells appears to be a factor of poor prognosis. Hormones are intimately involved in the development of prostatic cancer and are an integral part of its treatment. Progress in molecular biology has furthered out knowledge of this disease. In particular, growth factors such as EGF and FGF are particularly involved and are starting to have a clinical application. The oncogene and anti-oncogene system is currently being explored (particularly p53 abd BCL 2). They are the basis for carcinogenesis and analysis of these factors will allow a better approach to the mechanisms of tumour induction and development.
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PMID:[Cancer of the prostate. 2. Physiology and cellular development]. 771 57

We studied the interactions of phosphorothioate oligodeoxynucleotides and heparin-binding growth factors. By means of a gel mobility shift assay, we demonstrated that phosphodiester and phosphorothioate homopolymers bound to basic fibroblast growth factor (bFGF). Binding of a probe phosphodiester oligodeoxynucleotide could also be shown for other proteins of the FGF family, including acidic fibroblast growth factor (aFGF), Kaposi's growth factor (FGF-4) as well as for the bFGF-related vascular endothelial growth factor, VEGF. No binding to epidermal growth factor (EGF) was observed. In addition, using a radioreceptor assay, we have shown that phosphorothioate homopolymers of cytidine and thymidine blocked binding of not only 125I-bFGF, but also of 125I-PDGF to NIH 3T3 cells, whereas phosphodiester oligodeoxynucleotides were ineffective. The extent of blockade of binding was dependent on the chain length of the phosphorothioate oligodeoxynucleotide. Furthermore, we have examined the effects of 18-mer phosphorothioate oligodeoxynucleotides of different sequences on 125I-bFGF binding to low and high affinity sites on both NIH 3T3 fibroblasts and DU-145 prostate cancer cells. Despite the fact that we have observed inhibition of bFGF binding by the 18-mer phosphorothioate oligodeoxynucleotides for both the high and low affinity classes of bFGF receptor, the inhibition was sequence-selective only for the high affinity receptors. We have also demonstrated that phosphorothioate homopolymers of cytidine and thymidine release bFGF bound to low affinity receptors in extracellular matrix (ECM). Finally, the most potent phosphorothioate oligodeoxynucleotides used in these experiments (e.g. SdC28) were inhibitors of bFGF-induced DNA synthesis in NIH 3T3 cells.
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PMID:Phosphorothioate oligodeoxynucleotides bind to basic fibroblast growth factor, inhibit its binding to cell surface receptors, and remove it from low affinity binding sites on extracellular matrix. 785 27

Androgen receptor is necessary for the proliferation of androgen-dependent tumors including human prostatic cancer and murine androgen-sensitive tumors. However, androgen-independent tumor containing functional androgen receptor was observed in CS 2 cells, which is a subline of androgen-dependent mouse tumor (SC 115). CS 2 showed a new expression of hst-1, the product of which is a family of FGF. CS 2 secreted a growth factor which promotes growth of CS 2 and original SC 115 in an autocrine and paracrine manner. The role of oncogene(s) and suppressor gene(s) on the progression of the tumor is discussed.
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PMID:[Androgen-dependent tumor]. 844 42

Peptide growth factors play a role in the maintenance of normal prostatic growth and differentiation (Fig. 2). It seems likely that the androgen sensitivity of human prostate is mediated by the production of peptide growth factors from stromal cells which act as the direct intermediate of androgen action on epithelial cells. TGF-beta 1 inhibition of epithelial cells is opposed by the stimulatory action of EGF, IGF and FGFs to maintain an equilibrium of epithelial cell numbers. The indirect mitogenic action of androgens appear to act by down-regulation of TGF-beta 1 and possibly EGF receptors. There is also interaction with the effects of IGF-II, produced by prostatic stromal cells and acting on epithelial cells to increase proliferation. The growth of normal prostatic fibroblasts is under the control of bFGF and TGF-beta 1. However, although our understanding of the actions of these growth factors in the normal prostate has improved over the last decade, their role in the development and maintenance of prostate cancer is less clearly defined. TGF-beta 1, classically considered to be inhibitory for epithelial cells, may be up-regulated in prostatic tumours, stimulating growth. Alternatively, autocrine production of such growth factors by tumour cells may lead to loss of inhibitory effects from exogenous TGF-beta 1, a mechanism also witnessed with TGF-alpha and bFGF. The role of EGF in the development of prostate cancer is confusing because results from the use of different cell types and experimental conditions is contradictory. It may be that a switch in the production of the predominant EGFr ligand from EGF to TGF-alpha is an important feature in the development and maintenance of the malignant phenotype. The presence of TGF-alpha autocrine loops has been shown clearly in some tumour cell lines. This switch in the production of a particular ligand may also be a feature of IGFs in prostate cancer. IGF-II may be replaced by IGF-I during malignant progression, both of which are able to act via the type 1 receptor. This change in IGF expression appears to be accompanied by altered expression of the IGF-BP2, with less detectable within prostatic tissues but elevated serum levels [58]. Basic FGF is normally produced by prostatic fibroblasts but is also produced by some prostatic cancer cell lines [64]. However, as with all growth factors, the expression of the bFGF protein and its receptor is dependent on the cell line examined. The autocrine and paracrine control of normal and abnormal prostatic growth by growth factors is important in determining their role in the development and maintenance of prostate cancer. Better understanding of such mechanisms is essential for the development of novel therapeutic strategies in the control and treatment of prostate cancer.
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PMID:Peptide growth factors in the prostate as mediators of stromal epithelial interaction. 868 1


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