Cultured human prostate‐derived fibroblasts produce a factor that stimulates their growth with properties indistinguishable from basic fibroblast growth factor

Story, Michael T.; Livingston, Bonnie; Baeten, Laurie A.; Swartz, Susan J.; Jacobs, Stephen C.; Begun, Frank P.; Lawson, Russell K.

doi:10.1002/pros.2990150408

Cited by 95 publications

(50 citation statements)

References 16 publications

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“…The stimulation of tumour cell growth in conditioned medium is consistent with the secretion of stimulatory fibroblast derived growth factors and/or the inability to produce active growth inhibitory factors (Clemmons et al, 1981;Clemmons, 1984;Story et al, 1989;Yee et al, 1988). We have also shown a high proliferation effect of human skin tissue derived fibroblast C-SFM on MCF-7 cells.…”

Section: Discussionsupporting

confidence: 73%

Stromal influences on breast cancer cell growth

Roozendaal

Ooijen²,

Klijn³

et al. 1992

Br J Cancer

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Paracrine influences from fibroblasts derived from different sources of breast tissue on epithelial breast cancer cell growth in vitro were investigated. Medium conditioned (CM) by fibroblasts derived from tumours, adjacent normal breast tissue, and normal breast tissue obtained from reduction mammoplasty or from skin tissue significantly stimulated the growth of the steroid-receptor positive cell lines MCF-7 and ZR 75.1. The proliferation index (PI) on MCF-7 cells with CM from fibroblasts derived from breast tumour tissue was significantly higher than that obtained with fibroblasts derived from adjacent normal breast tissue (2p less than 0.05, n = 8). The PI obtained with CM from normal fibroblast cultures from reduction mammoplasty tissue, like normal tissue adjacent to the tumour, fell in the lower range of values. Skin fibroblast, like tumour tissue derived fibroblast, CM caused a high range PI. MDA-MB-231 and Evsa-T, two steroid-receptor negative cell lines, showed only a minor growth stimulatory responses with some of the fibroblast CM's. Evsa-T was occasionally inhibited by CM's. In conclusion, stromal factors play a role in the growth regulation of human breast cancer cells. The effects on cancer cell growth are, however, varying depending on the source of the stroma and the characteristics of the epithelial tumour cells.

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Section: Discussionsupporting

confidence: 73%

Stromal influences on breast cancer cell growth

Roozendaal

Ooijen²,

Klijn³

et al. 1992

Br J Cancer

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“…bFGF regulates cellular growth and differentiation by involving protein kinase C (Hrzenjak and Shain, 1997), mitogen-activated protein kinase (Hurley et al, 1996;Milasincic et al, 1996), phosphatidylinositol 3-kinase (Raffioni and Bradshaw, 1992) or phospholipase signalling (Sa and Fox, 1994;Suzuki et al, 1996). bFGF was identified as a major autocrine growth factor produced by prostate fibroblasts (Story et al, 1989). In later studies, it was demonstrated that prostate epithelial cells are also a source of bFGF (Nakamoto et al, 1992;Sherwood et al, 1992;Cronauer et al, 1997a).…”

Section: Discussionmentioning

confidence: 99%

Androgen receptor protein is down-regulated by basic fibroblast growth factor in prostate cancer cells

et al. 2000

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Interactions between polypeptide growth factors and the androgen receptor (AR) are important for regulation of cellular events in carcinoma of the prostate. Basic fibroblast growth factor (bFGF), the prototype of heparin-binding growth factors, and the AR are commonly expressed in prostate cancer. bFGF diminished prostate-specific antigen protein in the supernatants of androgen-stimulated human prostate cancer cells LNCaP by 80%. In the present study, we asked whether the bFGF effect on prostate-specific antigen is preceded by action on AR expression. LNCaP cells were treated with bFGF and AR protein expression was determined by immunoblotting and ligand binding assay. bFGF down-regulated AR protein in a dose-dependent manner showing a maximal effect at 50 ng ml −1 both in the presence or absence of dihydrotestosterone. Down-regulation of AR protein expression occurred already after 8 h of bFGF treatment and a maximal inhibition was observed 24 h after addition of bFGF to culture media. As AR expression can be reduced by an increase in intracellular calcium levels, we investigated whether the bFGF effect on AR protein is mediated by this mechanism. Calcium release from intracellular stores and store-operated calcium influx after treatment with either bFGF or calcium ionophore A 23187 were measured by single cell fluorescence technique. The ionophore A 23187 was able to induce calcium influx and an increase in cytoplasmic calcium concentration in LNCaP cells. In contrast, bFGF was incapable of eliciting a similar effect. In contrast to AR protein, AR mRNA levels were not affected by bFGF as shown by semiquantitative reverse transcription polymerase chain reaction. In summary, these studies show that bFGF is a potent negative regulator of AR protein expression in the human prostate cancer cell line LNCaP. © 2000 Cancer Research Campaign

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“…It has been demonstrated that urogenital sinus mesenchyme plays a major role in the (androgen-induced) development of the gland (Cunha et al, 1987); subsequently it was shown that these interactions may have retained their integral role in the adult prostate (Cunha et al, 1987;Chung et al,1991a,b (Thompson, 1990;Story, 1991), and some of these have been positively identified as being produced (also) by stromal cells, suggesting a role in stromal-epithelial interactions (Story et al, 1989;Djakiew et al, 1991;Gleave et al, 1992). The fact, however, that prolonged androgen administration to castrated animals does not induce the gland to grow beyond its predetermined size (Sugimura et al, 1986), together with the observation that withdrawal of androgens decreases epithelial cell number only in the in vivo situation where stroma is present (Isaacs, 1984;McKeehan et al, 1984), suggests a role for stromally derived epithelial cell growth inhibitors.…”

Section: Discussionmentioning

confidence: 99%

Stromal inhibition of prostatic epithelial cell proliferation not mediated by transforming growth factor beta

Kooistra

Raaij²,

Klaij³

et al. 1995

Br J Cancer

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Summary The paracrine influence of prostatic stroma on the proliferation of prostatic epithelial cells was investigated. Stromal cells from the human prostate have previously been shown to inhibit anchoragedependent as well as anchorage-independent growth of the prostatic tumour epithelial cell lines PC-3 and LNCaP. Antiproliferative activity, mediated by a diffusible factor in the stromal cell conditioned medium, was found to be produced specifically by prostatic stromal cells. In the present study the characteristics of this factor were examined. It is demonstrated that prostate stroma-derived inhibiting factor is an acid-and heat-labile, dithiothreitol-sensitive protein. Although some similarities with type beta transforming growth factor (TGF-P)-like inhibitors are apparent, evidence is presented that the factor is not identical to TGF-J3 or to the TGF-p-like factors activin and inhibin. Absence of TGF-P activity was shown by the lack of inhibitory response of the TGF-p-sensitive mink lung cell line CCL-64 to prostate stromal cell conditioned medium and to concentrated, partially purified preparations of the inhibitor. Furthermore, neutralising antibodies against TGF-PI or TGF-P2 did not cause a decline in the level of PC-3 growth inhibition caused by partially purified inhibitor. Using Northern blot analyses, we excluded the involvement of inhibin or activin. It is concluded that the prostate stroma-derived factor may be a novel growth inhibitor different from any of the currently described inhibiting factors.

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Cultured human prostate‐derived fibroblasts produce a factor that stimulates their growth with properties indistinguishable from basic fibroblast growth factor

Cited by 95 publications

References 16 publications

Stromal influences on breast cancer cell growth

Stromal influences on breast cancer cell growth

Androgen receptor protein is down-regulated by basic fibroblast growth factor in prostate cancer cells

Stromal inhibition of prostatic epithelial cell proliferation not mediated by transforming growth factor beta

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