Analysis of microdissected prostate tissue with ProteinChip® arrays - a way to new insights into carcinogenesis and to diagnostic tools

Wellmann, Axel; Wollscheid, Volker; Lu, Hong; Zhan, Lu; Albers, Peter; Schütze, Karin; Rohde, V.; Behrens, P.; Dreschers, Stefan; Ko, Yon; Wernert, Nicolas

doi:10.3892/ijmm.9.4.341

Cited by 46 publications

(40 citation statements)

References 9 publications

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“…Prostate fibroblasts can influence prostate carcinoma cell growth by modifying proliferation or apoptosis via paracrine mechanisms (38)(39)(40)(41). Using SELDI-TOF mass spectrometry we found a number of differences in gene expression at the proteome level not only between normal and neoplastic epithelial cells but also between normal and peritumoural stromal cells (42).…”

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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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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“…That group and others have applied this approach to the detection of proteomic profiles in serum that distinguish not only ovarian cancer but also prostate (11) and breast cancer (12) patients from those without cancer. The availability of a relatively inexpensive, accurate blood test for the early diagnosis of most, if not all, cancers has generated great excitement among scientists and the public.…”

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confidence: 99%

Detection of cancer-specific markers amid massive mass spectral data

Zhu

Wang

et al. 2003

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

158

104

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We propose a comprehensive pattern recognition procedure that will achieve best discrimination between two or more sets of subjects with data in the same coordinate system. Applying the procedure to MS data of proteomic analysis of serum from ovarian cancer patients and serum from cancer-free individuals in the Food and Drug Administration͞National Cancer Institute Clinical Proteomics Database, we have achieved perfect discrimination (100% sensitivity, 100% specificity) of patients with ovarian cancer, including early-stage disease, from normal controls for two independent sets of data. Our procedure identifies the best subset of proteomic biomarkers for optimal discrimination between the groups and appears to have higher discriminatory power than other methods reported to date. For large-scale screening for diseases of relatively low prevalence such as ovarian cancer, almost perfect specificity and sensitivity of the detection system is critical to avoid unmanageably high numbers of false-positive cases. discriminant analysis ͉ random field ͉ resampling ͉ statgram

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“…One section was mounted on conventional slides and stained with hematoxylin and eosin (H&E) for diagnostic evaluation by an experienced pathologist who confirmed the absence of prostate carcinoma in the two zones. Laser microdissection was performed as previously described (23)(24)(25). Frozen sections were dried for 2 min in the cryotome, washed for 2 min with 70% ethanol in DEPC-treated water and stained for 30 sec in 1% cresyl violet diluted in 50% ethanol-DEPC-treated water.…”

Section: Methodsmentioning

confidence: 99%

The peripheral zone of the prostate is more prone to tumor development than the transitional zone: Is the ETS family the key?

Wernert

2011

Mol Med Report

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Abstract. Predisposition to develop prostate cancer (PCA) varies among the prostate zones, with the peripheral zone (PZ) more prone to tumor development than the transitional zone (TZ). In view of the fact that molecular differences between the zones may explain this difference, combined with the findings that translocations between TMPRSS2 and several ETS members are frequently observed in PCA, we hypothesized that the ETS family may be crucial to explaining this difference. Normal tissues from the PZ and the TZ of 20 PCA patients were laser microdissected to separate glands from stroma. Two oligo microarrays were performed in order to investigate the variation in ETS family gene expression between the glands and the stroma of the two zones. The ETS members, ELF-3, ELF-5, ERG, ETV-1, ETV-4, ETV-5, ETV-7 and FEV, were found to be differentially expressed. A striking observation was that ERG and ETV-1 were found to be up-regulated in the glands of the PZ compared to the TZ, particularly when considering that ERG and ETV-1 fusions account for 50-80% and 20% of PCA occurrences, respectively. These results indicate that the glands and stroma of the two zones display distinct molecular differences and zonal-specific expression of ETS members. Furthermore, ETS members up-regulated in PCA are already overexpressed in the normal PZ, suggesting that these members play a role in the development and progression of PCA. IntroductionProstate cancer (PCA) is a clinically heterogeneous and often multifocal disease with a clinical outcome that is difficult to predict (1,2). Therefore, advancements in the knowledge of the molecular basis of PCA should improve the prediction of prognosis, as genetic aberrations drive the formation and aggressiveness of prostate carcinoma (3).The prostate is supported by a stroma and can be divided into three anatomical zones: peripheral (the so-called prostate proper), transitional and central zones (4,5). The predisposition to develop PCA is different among these zones, as most manifest PCAs (75%) occur in the peripheral zone (PZ), at the dorsal and dorso-lateral side of the prostate, while only some (20%) occur in the transitional zone (TZ) (6,7).The latter cancers are mostly so-called incidental carcinomas with a nonaggressive clinical course, whereas cancers from the PZ are more aggressive, tend to invade the periprostatic tissues and have higher biochemical recurrence rates (6,8). The molecular basis underlying the differences in the susceptibility to PCA between the different zones of the prostate remains unknown. However, it has been suggested that some of the differences in susceptibility may have an embryological basis (9). As PCA rarely develops in the central zone compared with the PZ, it has been suggested that the central zone is derived from the Wolffian duct, the same duct from which the seminal vesicle is derived, and in contrast to the remainder of the prostate, which is derived from the urogenital sinus (5,9,10).In contrast to these varying predispositions of the TZ and the PZ t...

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Analysis of microdissected prostate tissue with ProteinChip® arrays - a way to new insights into carcinogenesis and to diagnostic tools

Cited by 46 publications

References 9 publications

Tumour-stroma interactions between metastatic prostate cancer cells and fibroblasts

Tumour-stroma interactions between metastatic prostate cancer cells and fibroblasts

Detection of cancer-specific markers amid massive mass spectral data

The peripheral zone of the prostate is more prone to tumor development than the transitional zone: Is the ETS family the key?

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