FGF7/KGF triggers cell transformation and invasion on immortalised human prostatic epithelial PNT1A cells

Ropiquet, Frédéric; Huguenin, Sandra; Villette, Jean‐Marie; Ronflé, V; Brun, G; Maitland, Norman J.; Cussenot, Olivier; Fiet, Jean; Berthon, Philippe

doi:10.1002/(sici)1097-0215(19990719)82:2<237::aid-ijc14>3.3.co;2-h

Cited by 13 publications

(14 citation statements)

References 3 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This was well in line with an increase of anchorage-independent growth of DU-145 cells in soft agar assays after stimulation with fibroblast conditioned medium. In ELISA assays of fibroblast conditioned media we identified KGF as a known factor able to stimulate proliferation of normal and neoplastic prostate epithelial cells (66). The fact that all three metastatic prostate cancer cell lines secreted KGF similarly suggests again an autocrine effect on tumour cell proliferation.…”

Section: Discussionmentioning

confidence: 87%

Tumour-stroma interactions between metastatic prostate cancer cells and fibroblasts

Kaminski

Hahne²,

Haddouti³

et al. 2006

Int J Mol Med

View full text Add to dashboard Cite

Abstract.Previous work has shown the importance of tumourstroma interactions for prostate cancer development at the primary site. The aim of the present study was to find out whether evidence can be found for a tumour-stroma crosstalk also between metastatic prostate cancer cell lines and non-prostatic stromal fibroblasts which are encountered by metastatic cells at most sites. We addressed this issue in cell culture systems using 3 metastatic human prostate cancer cell lines (LnCaP, PC-3 and DU-145) on the one hand, and a human fibroblast line (HFF, human foreskin fibroblasts) on the other. We incubated fibroblasts with tumour cell-and tumour cells with fibroblast-conditioned media and evaluated several parameters important for the establishment of metastases such as cell proliferation, migration and expression of matrix degrading proteases. We also determined in the conditioned media the concentrations of several growth factors and cytokines which might be responsible for the observed effects. We found that media conditioned by all 3 metastatic prostate cancer cell lines stimulated fibroblast proliferation which corresponds to fibrous stroma induction in vivo. DU-145 cell conditioned media induced in fibroblasts expression of mmp-1 mRNA known to be important for tumour invasion. ELISA assays revealed that tumour cells secrete bFGF, PDGF and TNF· known to stimulate fibroblast proliferation and/or MMP-1 expression. Cultivation of DU-145 carcinoma cells in fibroblast conditioned medium resulted in an enhanced proliferation and anchorage-independent growth of this cell line in soft agar. Fibroblast conditioned medium also increased migration of PC-3 cells in the wound assay and slightly augmented mmp-1 expression. KGF (able to stimulate proliferation of normal and neoplastic prostate epithelial cells) was secreted by fibroblasts at higher concentrations than by all 3 tumour cell lines. In addition, fibroblasts secreted TNF·, bFGF, PDGF, HGF and also VEGF, the most important factor for tumour vascularization. Our results provide evidence that tumour-stroma interactions do not only exist at the primary site but also between metastatic prostate cancer cell lines and their fibroblastic microenvironment. These interactions, which are mediated through secreted factors, affect several steps of the metastatic cascade including proliferation, anchorage-independent growth, migration and the secretion of matrix-degrading proteases.

show abstract

Section: Discussionmentioning

confidence: 87%

Tumour-stroma interactions between metastatic prostate cancer cells and fibroblasts

Kaminski

Hahne²,

Haddouti³

et al. 2006

Int J Mol Med

View full text Add to dashboard Cite

show abstract

“…Such increases in invasion were attributed to both increased expression of hepatocyte growth factor and matrix metalloproteinase production. It may be considered unusual that stromal cells can stimulate non-malignant epithelial cell invasion (though the number of actual cells invading was small), but a similar modulation of invasive capacity can be achieved with the PNT1a cells by transfection of a keratinocyte growth factor cDNA (Ropiquet et al, 1999). In this system the expression of KGF, which is expressed exclusively by fibroblasts in normal prostatic tissues, stimulated both PNT1a cell invasion through matrigel invasion chambers and the production of matrix metalloproteinase 1 and plasminogen activator, although the cells remained non-malignant in vivo.…”

Section: Discussionmentioning

confidence: 99%

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

2000

View full text Add to dashboard Cite

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.

show abstract

“…FGF family members possess broad mitogenic and cell survival activities, and are involved in a variety of biological processes, including tumor growth and invasion. FGF7 is a potent epithelial cellspecific growth factor, and is involved in tumorigenesis through stimulating proliferation and invasion (Ropiquet et al, 1999;Shaoul et al, 2006). These findings raised the possibility that IRX1 overexpression downregulated expression of BDKRB2, FGF7 and HIST2H2BE, consequently inhibiting angiogenesis, cell proliferation and invasion in gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

Homeobox gene IRX1 is a tumor suppressor gene in gastric carcinoma

et al. 2010

View full text Add to dashboard Cite

The IRX1 tumor suppressor gene is located on 5p15.33, a cancer susceptibility locus. Loss of heterozygosity of 5p15.33 in gastric cancer was identified in our previous work. In this study, we analyzed the molecular features and function of IRX1. We found that IRX1 expression was lost or reduced in gastric cancer. However, no mutations were identified in IRX1-encoding regions. IRX1 transcription was suppressed by hypermethylation, and the expression of IRX1 mRNA was partially restored in gastric cancer cells after 5-Aza-dC treatment. Restoring IRX1 expression in SGC-7901 and NCI-N87 gastric cancer cells inhibited growth, invasion and tumorigenesis in vitro and in vivo. We identified a number of target genes by global microarray analysis after IRX1 transfection combined with real-time PCR and chromatin immunoprecipitation assay. BDKRB2, an angiogenesis-related gene, HIST2H2BE and FGF7, cell proliferation and invasionrelated genes, were identified as direct IRX1 target genes. The hypermethylation of IRX1 was not only detected in primary gastric cancer tissues but also in the peripheral blood of gastric cancer patients, suggesting IRX1 could potentially serve as a biomarker for gastric cancer.

show abstract

FGF7/KGF triggers cell transformation and invasion on immortalised human prostatic epithelial PNT1A cells

Cited by 13 publications

References 3 publications

Tumour-stroma interactions between metastatic prostate cancer cells and fibroblasts

Tumour-stroma interactions between metastatic prostate cancer cells and fibroblasts

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

Homeobox gene IRX1 is a tumor suppressor gene in gastric carcinoma

Contact Info

Product

Resources

About