Stromal cells from human benign prostate hyperplasia produce a growth-inhibitory factor for LNCaP prostate cancer cells, identified as interleukin-6

Degeorges, Armelle; Tatoud, Roger; Fauvel-Lafève, Françoise; Podgorniak, Marie-Pierre; Millot, Guy; Crémoux, Patricia de; Calvo, Fabien

doi:10.1002/(sici)1097-0215(19961009)68:2<207::aid-ijc12>3.0.co;2-7

Cited by 90 publications

(39 citation statements)

References 30 publications

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“…However, the results presented here and those found previously (Lang et al, 1998) do not support this hypothesis. Our results, using a mixed population of stromal cells, would agree with both the theories that fibroblasts can stimulate (Kabalin et al, 1989;Gleave et al, 1991) or inhibit (Kooistra et al, 1995a;Degeorges et al, 1996) epithelial cell growth when compared to growth on tissue culture plastic. However, the majority of stromal cultures had no effect on, or inhibited epithelial cell growth.…”

Section: Discussionsupporting

confidence: 91%

“…In vitro models have shown that primary cultures of prostatic stromal cells can stimulate epithelial growth derived from normal and malignant tissue (Kabalin et al, 1989) but also that prostate fibroblasts derived from normal and malignant tissue inhibit or have mixed effects on epithelial growth (Konig et al, 1987;Kooistra et al, 1995a;Degeorges et al, 1996). In vivo models indicate that whilst rat prostate tumour fibroblasts can stimulate LNCaP tumour cell growth, embryonic mouse fibroblasts had no effect (Camps et al, 1990;Gleave et al, 1991).…”

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confidence: 99%

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In vitro modelling of epithelial and stromal interactions in non-malignant and malignant prostates

2000

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SummaryTo study the effects of stromal epithelial cell interactions on prostate cancer metastasis, we have used primary human prostatic stromal cells derived from malignant and non-malignant tissues and established epithelial cell lines from normal (PNT1a and PNT2-C2) and tumour (PC-3, DU145 and LNCaP) origins. The effects of stromal cells on epithelial cell growth were studied in direct and indirect (using culture inserts) co-culture and by exposure to stromal cell-conditioned medium (assessed by MTT assay). The influence of stromal cells on epithelial cell invasion was measured using matrigel invasion chambers and on epithelial cell motility using time lapse microscopy. Results indicated that epithelial cell line growth was similarly unaffected or inhibited by stromal cells derived from malignant (n = 8) or non-malignant tissue (n = 8). In contrast, PNT2-C2 and PC-3 cells were found to be the least and the most invasive and motile epithelia respectively. Stromal cultures enhanced the invasion of both epithelial cells, but no differences were observed between the use of malignant and non-malignant tissues. All stromal cultures modestly stimulated PNT2-C2 motility but displayed a greater stimulation of PC-3 cell motility, while stromal cells derived from malignant tissue stimulated PNT2-C2 and PC-3 cell motility more than stromal cultures from non-malignant tissues.

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Section: Discussionsupporting

confidence: 91%

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confidence: 99%

In vitro modelling of epithelial and stromal interactions in non-malignant and malignant prostates

2000

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“…Chung et al showed that IL-6 promoted cell growth of hormone-refractory cells but had no effect on the growth of hormone-dependent cell lines (4). Addition of exogenous IL-6 to the culture media of LNCaP cells by several groups has resulted in a dose-dependent inhibition of cell growth with development of a neuroendocrine cell phenotype (4,(18)(19)(20)(21)(22). On the other hand, some researchers observed a stimulatory response after treatment with IL-6 (23,24).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Interleukin-6 with CNTO328, an Anti-Interleukin-6 Monoclonal Antibody, Inhibits Conversion of Androgen-Dependent Prostate Cancer to an Androgen-Independent Phenotype in Orchiectomized Mice

et al. 2006

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Initially, prostate cancer is androgen dependent. However, most cases progress to an androgen-independent state through unknown mechanisms. Interleukin-6 (IL-6) has been associated with prostate cancer progression including activation of the androgen receptor (AR). To determine if IL-6 plays a role in the conversion of prostate cancer from androgen dependent to androgen independent, we established androgen-dependent LuCaP 35 human prostate cancer xenografts in nude mice, castrated the mice, and blocked IL-6 activity using a neutralizing antibody (CNT0328) for a period of 18 weeks. IL-6 inhibition increased survival of mice and inhibited tumor growth, as reflected by decreased tumor volume and prostatespecific antigen levels, compared with that in mice receiving isotype control antibody. To test the effect of IL-6 inhibition on the conversion from androgen dependent to androgen independent, tumor cells from the treated mice were assessed for their androgen dependence both in vitro and by implanting them into sham-operated or orchiectomized mice. Tumor cells derived from the isotype-treated animals converted to androgen-independent state, whereas tumor cells from the anti-IL-6 antibody-treated mice were still androgen dependent in vitro and in vivo. Although there was no difference in AR levels between the androgen-independent and androgen-dependent tumors, IL-6 inhibition promoted both apoptosis and inhibited cell proliferation in tumors and blocked the orchiectomyinduced expression of histone acetylases, p300 and CBP, which are AR cofactors. These data show that IL-6 contributes to the development of androgen independence in prostate cancer and suggest that it mediates this effect, in part, through modulation of p300 and CBP. (Cancer Res 2006; 66(6): 3087-95)

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“…This could explain the favourable prognosis associated with the presence of tumour IL-6 in early-stage breast cancer (Karczewska et al, 2000) and the poor survival associated with high serum IL-6 levels in this series of metastatic breast cancer patients. It is noteworthy that, as in early-stage breast cancer, IL-6 functions as an inhibitor of cancer cell growth in benign prostate hyperplasia (Degeorges et al, 1996), but is correlated with a poor survival in stage-D prostate cancer (Nakashima et al, 2000).…”

Section: Prognostic Value Of Angiogenic Factors In Breast Cancer T Bamentioning

confidence: 99%

Prognostic value of serum levels of interleukin 6 and of serum and plasma levels of vascular endothelial growth factor in hormone-refractory metastatic breast cancer patients

et al. 2003

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Prediction of survival for patients with metastatic breast cancer is often inaccurate and may be helped by new biological parameters. Tumour growth being angiogenesis-dependent, it has been hypothesised that the assessment of angiogenic factor production might reflect the clinical behaviour of cancer progression. This study was designed to investigate the clinical significance of vascular endothelial growth factor (VEGF) and interleukin 6 (IL-6) in hormone-refractory metastatic breast cancer. Serum and plasma concentrations of VEGF and serum concentration of IL-6 were measured in 87 patients with a fully documented history of metastatic breast cancer using an enzyme-linked immunoassay. All patients had detectable levels of VEGF, whereas 39% patients had detectable serum levels of IL-6. There was a positive correlation between IL-6 levels and the theoretical VEGF load of platelets (Po0.001). The presence of high levels of serum IL-6, but not VEGF, was significantly correlated to a shorter survival. In a multivariate analysis along with clinical prognostic parameters, serum IL-6 was identified as an independent adverse prognostic variable for overall survival (Po0.001). These results indicate that serum IL-6 levels correlate to poor survival in patients with hormone-refractory metastatic breast cancer. Vascular endothelial growth factor serum and plasma levels are not useful indicators of prognosis for these patients.

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Stromal cells from human benign prostate hyperplasia produce a growth-inhibitory factor for LNCaP prostate cancer cells, identified as interleukin-6

Cited by 90 publications

References 30 publications

In vitro modelling of epithelial and stromal interactions in non-malignant and malignant prostates

In vitro modelling of epithelial and stromal interactions in non-malignant and malignant prostates

Inhibition of Interleukin-6 with CNTO328, an Anti-Interleukin-6 Monoclonal Antibody, Inhibits Conversion of Androgen-Dependent Prostate Cancer to an Androgen-Independent Phenotype in Orchiectomized Mice

Prognostic value of serum levels of interleukin 6 and of serum and plasma levels of vascular endothelial growth factor in hormone-refractory metastatic breast cancer patients

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