Dysregulated expression of growth factors and their receptors in the development of prostate cancer

Djakiew, Daniel

doi:10.1002/(sici)1097-0045(20000201)42:2<150::aid-pros10>3.0.co;2-h

Cited by 157 publications

(103 citation statements)

References 132 publications

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“…Several protein tyrosine kinases, such as PDGF receptor (PDGF-R), c-met, HER-2͞neu, and IGF-1R, are expressed in prostate cancer, including metastatic sites (2). CSF-1R is more closely related structurally to the receptors for PDGF than to other PTK receptor subfamilies (54).…”

Section: Discussionmentioning

confidence: 92%

Expression of colony-stimulating factor 1 receptor during prostate development and prostate cancer progression

Ide

Seligson²,

Memarzadeh³

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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Section: Discussionmentioning

confidence: 92%

Expression of colony-stimulating factor 1 receptor during prostate development and prostate cancer progression

Ide

Seligson²,

Memarzadeh³

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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“…In cancer of the prostate (CaP), multiple growth factor systems, including FGF, EGF, VEGF and IGF families, contribute to tumorigenesis (Djakiew, 2000).…”

Section: Introductionmentioning

confidence: 99%

“…FGF8 expression in resected prostate cancer specimens is significantly associated with tumour grade and stage, with high levels of FGF8 expression predicting aggressive disease with poorer disease-specific survival (Dorkin et al, 1999). Malignant epithelial cells exhibit autocrine growth stimulation, including expression of EGF and related family members such as transforming growth factor-a (TGF-a) (Djakiew, 2000). This autocrine expression circumvents the paracrine dependence on stromal-derived factors and contributes to the autonomous growth in prostate cancer.…”

Section: Introductionmentioning

confidence: 99%

Epigenetic inactivation of the human sprouty2 (hSPRY2) homologue in prostate cancer

et al. 2005

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Abnormal signalling events mediated by receptor tyrosine kinases (RTKs) contribute to human carcinogenesis. Sprouty2 (Spry2) is a key antagonistic regulator of RTK signalling and suppression of its expression or function may facilitate proliferation and angiogenesis. Using prostate cancer (CaP) as a model, we investigated the significance of Spry2 in human malignancy. We observed downregulated Spry2 expression in invasive CaP cell lines and high-grade clinical CaP (compared to benign prostatic hyperplasia (BPH) and well-differentiated tumours, P ¼ 0.041). A large CpG island is associated with hSPRY2, and extensive hypermethylation of this CpG island was observed in 76-82% of high-grade CaP, while control BPH tissues were predominantly unmethylated (P ¼ 0.0005). Furthermore, suppressed Spry2 expression correlated with methylation of the CpG region in clinical samples (P ¼ 0.004) and treatment with 5-aza-2 0 -deoxycytidine reactivated Spry2 expression in LNCaP and PC-3M cells. hSPRY2 maps to the long arm of chromosome 13 (13q31.1), where loss of heterozygosity (LOH) has been reported. We found no evidence of mutation; however, we demonstrated 27-40% LOH using flanking markers to hSPRY2. Hence, while biallelic epigenetic inactivation of hSPRY2 represents the main genetic event in prostate carcinogenesis, the observed 27-40% LOH presents evidence of hemizygous deletion with the remaining allele hypermethylated. We therefore propose hSPRY2 as a potential tumour suppressor locus in CaP.

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“…Linkage analyses point to hereditary prostate cancer genes (6,7) and polymorphisms of so-called modifier genes (related to hormone response, cell protection or DNA repair) may increase the risk of prostate carcinoma (7)(8)(9). Several proto-oncogenes such as myc (10), EIF3S3 (11), bcl2 (12) or growth factor encoding genes (13) have been identified. TP53 (14) and PTEN (15) are among tumour suppressor genes shown to be inactivated in prostate cancer.…”

Section: Introductionmentioning

confidence: 99%

Tumour-stroma interactions between metastatic prostate cancer cells and fibroblasts

Kaminski

Hahne²,

Haddouti³

et al. 2006

Int J Mol Med

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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.

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Dysregulated expression of growth factors and their receptors in the development of prostate cancer

Cited by 157 publications

References 132 publications

Expression of colony-stimulating factor 1 receptor during prostate development and prostate cancer progression

Expression of colony-stimulating factor 1 receptor during prostate development and prostate cancer progression

Epigenetic inactivation of the human sprouty2 (hSPRY2) homologue in prostate cancer

Tumour-stroma interactions between metastatic prostate cancer cells and fibroblasts

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