Stromal–epithelial interactions influence prostate cancer cell invasion by altering the balance of metallopeptidase expression

Dawson, Louise A.; Maitland, Norman J.; Turner, Anthony J.; Usmani, Badar A.

doi:10.1038/sj.bjc.6601717

Cited by 40 publications

(45 citation statements)

References 23 publications

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“…Invasion assay The invasion assay was performed essentially as described by Dawson et al (2004). Briefly, invasion chambers were prepared using matrigel (250 mg ml À1 ), which was added (200 ml) to cell culture inserts (8 mm pore) and incubated overnight at 371C.…”

Section: Methodsmentioning

confidence: 99%

“…PNT1-a, a low-invasive cell line (Lang et al, 2000;Dawson et al, 2004), which expresses negligible ECE-1 (Dawson et al, 2004) was transiently transfected with the ECE-1 isoforms, and invasion through matrigel was measured. Transient expression of ECE-1c in PNT1-a cells increased invasion by 100% in the presence of untreated stromal cells, compared with untransfected PNT1-a (Figure 4).…”

Section: Endothelin-converting Enzyme 1c Isoform Can Transform Low-inmentioning

confidence: 99%

“…We have previously demonstrated that ECE-1 is present in PC cell lines and primary tissues, and is expressed at the cell surface and intracellularly (Dawson et al, 2004(Dawson et al, , 2006, with levels of ECE-1 elevated in primary malignant stromal cells as compared with benign (Dawson et al, 2004). The specific inhibition of endogenous ECE-1 activity in these stromal cells significantly reduced epithelial cell invasion (Dawson et al, 2004).…”

mentioning

confidence: 99%

“…We and others have shown that ECE-1 expression is significantly elevated in tumours (Ahmed et al, 2000;Eberl et al, 2000;Egidy et al, 2000b;Arun et al, 2001;Usmani et al, 2002;Dawson et al, 2004Dawson et al, , 2006Awano et al, 2005;Smollich et al, 2007). We have previously demonstrated that ECE-1 is present in PC cell lines and primary tissues, and is expressed at the cell surface and intracellularly (Dawson et al, 2004(Dawson et al, , 2006, with levels of ECE-1 elevated in primary malignant stromal cells as compared with benign (Dawson et al, 2004). The specific inhibition of endogenous ECE-1 activity in these stromal cells significantly reduced epithelial cell invasion (Dawson et al, 2004).…”

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confidence: 99%

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Isoforms of endothelin-converting enzyme-1 (ECE-1) have opposing effects on prostate cancer cell invasion

et al. 2008

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Cross-talk between tumour and stromal cells can profoundly influence cancer cell invasion by increasing the availability of mitogenic peptides such as endothelin-1 (ET-1). Endothelin-1 is elevated in men with metastatic prostate cancer (PC), and can exert both an autocrine (epithelial) and a paracrine (stromal) influence on growth. Endothelin-1 is generated from its inactive precursor big-ET-1 by endothelin-converting enzyme 1 (ECE-1). We and others have demonstrated that ECE-1 expression is significantly elevated in tumours and surrounding stromal tissue. Our current data show siRNA-mediated knockdown of stromal ECE-1 reduces epithelial (PC-3) cell invasion in coculture. Interestingly, readdition of ET-1 only partially recovers this effect suggesting a novel role for ECE-1 independent of ET-1 activation. Parallel knockdown of ECE-1 in both stromal and epithelial compartments results in an additive decrease in cell invasion. We extrapolated this observation to the four recognised isoforms ECE-1a, ECE-1b, ECE-1c and ECE-1d. Only ECE-1a and ECE-1c were significant but with reciprocal effects on cell invasion. Transient ECE-1c overexpression increased PC-3 invasiveness through matrigel, whereas transient ECE-1a expression suppressed invasion. Furthermore, transient ECE-1a expression in stromal cells strongly counteracts the effect of transient ECE-1c expression in PC-3 cells. The ECE-1 isoforms may, therefore, be relevant targets for antiinvasive therapy in prostate and other cancers.

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Section: Methodsmentioning

confidence: 99%

Section: Endothelin-converting Enzyme 1c Isoform Can Transform Low-inmentioning

confidence: 99%

mentioning

confidence: 99%

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Isoforms of endothelin-converting enzyme-1 (ECE-1) have opposing effects on prostate cancer cell invasion

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“…[4][5][6] Loss of NEP in prostate cancer cell lines results in increased peptide-mediated cell growth, cell migration and invasion, and ligandindependent activation of the insulin-like growth factor-1 receptor leading to Akt phosphorylation. 4,7,8 Loss of NEP in vivo in primary prostate cancers correlates with increased Akt phosphorylation, and predicts biochemical relapse in patients who have undergone radical prostatectomy. 6,9 Together, these studies suggest that NEP loss contributes to prostate cancer progression.…”

Section: Introductionmentioning

confidence: 99%

Neutral endopeptidase inhibits prostate cancer tumorigenesis by reducing FGF-2-mediated angiogenesis

Horiguchi

Chen

Goodman

et al. 2007

Prostate Cancer Prostatic Dis

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Neutral endopeptidase (NEP) is a cell surface peptidase that catalytically inactivates a variety of physiologically active peptides including basic fibroblast growth factor (FGF-2). We investigated the effect of using lentivirus to overexpress NEP in NEP-deficient DU145 prostate cancer cells. Third-generation lentiviral vectors encoding wild-type NEP (L-NEP), catalytically inactive mutant NEP (L-NEPmu), and green fluorescent protein (L-GFP) were stably introduced into DU145 cells. FGF-2 levels in cell culture supernatants decreased by 80% in L-NEP-infected DU145 cells compared to cells infected with L-NEPmu or L-GFP (Po0.05) while levels of other angiogenic factors were not altered. In vitro tubulogenesis of human vascular endothelial cells induced by conditioned media from DU145 cells infected with L-NEP was significantly reduced compared with that from DU145 cells infected with L-GFP (Po0.05). Tumor xenografts from L-NEP-infected DU145 cells were significantly smaller compared to control cell xenografts and vascularity within these tumors was decreased (Po0.05). Our data suggest that stable expression of NEP in DU145 cells inhibits prostate cancer tumorigenicity by inhibiting angiogenesis, with a probable mechanism being proteolytic inactivation of FGF-2.

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Endothelin system in oral squamous carcinoma cells: Specific siRNA targeting of ECE‐1 blocks cell proliferation

Awano

Dawson

Hunter

et al. 2005

Intl Journal of Cancer

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The present study focused on the endothelin axis in human oral squamous cell carcinoma (SCC) cells. We investigated the expression and distribution of endothelin-1 (ET-1), its receptors (endothelin-A receptor (ET A R) and endothelin-B receptor (ET B R)) and isoforms of its specific converting enzyme 1b, 1c) and the report on their relative influences on cell proliferation. We also investigated the effect of an ECE-specific inhibitor (ECE-i) and siRNA targeting of the ECE-1 gene on SCC cell proliferation. We observed the expression of ET-1, ET A R, ET B R and all endothelin-converting enzyme-1 (ECE-1) isoforms in oral SCC cells, but only the expression of ET-1, ET B R and ECE-1 was increased when compared to normal human epidermal keratinocytes. ET-1 alone stimulated proliferation of oral SCC cells. Antagonists of either ET A R or ET B R inhibited ET-1-mediated proliferation. Decreased ECE-1 expression after ECE siRNA treatment reduced SCC cell proliferation. Antiproliferative effects were also observed by inhibiting ECE activity with ECE-i. In conclusion, the present study demonstrates that modulation of the endothelin system in oral SCC cells might provide a novel therapeutic protocol for oral cancer. ' 2005 Wiley-Liss, Inc.

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Stromal–epithelial interactions influence prostate cancer cell invasion by altering the balance of metallopeptidase expression

Cited by 40 publications

References 23 publications

Isoforms of endothelin-converting enzyme-1 (ECE-1) have opposing effects on prostate cancer cell invasion

Isoforms of endothelin-converting enzyme-1 (ECE-1) have opposing effects on prostate cancer cell invasion

Neutral endopeptidase inhibits prostate cancer tumorigenesis by reducing FGF-2-mediated angiogenesis

Endothelin system in oral squamous carcinoma cells: Specific siRNA targeting of ECE‐1 blocks cell proliferation

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