BACKGROUND: Nodular melanoma is one of the most life threatening tumors with still poor therapeutic outcome. Similarly to other tumors, permissive microenvironment is essential for melanoma progression. Features of this microenvironment are arising from molecular crosstalk between the melanoma cells (MC) and the surrounding cell populations in the context of skin tissue. Here, we study the effect of melanoma cells on human primary keratinocytes (HPK). Presence of MC is as an important modulator of the tumor microenvironment and we compare it to the effect of nonmalignant lowly differentiated cells also originating from neural crest (NCSC). METHODS: Comparative morphometrical and immunohistochemical analysis of epidermis surrounding nodular melanoma (n = 100) was performed. Data were compared to results of transcriptome profiling of in vitro models, in which HPK were co-cultured with MC, normal human melanocytes, and NCSC, respectively. Differentially expressed candidate genes were verified by RT-qPCR. Biological activity of candidate proteins was assessed on cultured HPK. RESULTS: Epidermis surrounding nodular melanoma exhibits hyperplastic features in 90% of cases. This hyperplastic region exhibits aberrant suprabasal expression of keratin 14 accompanied by loss of keratin 10. We observe that MC and NCSC are able to increase expression of keratins 8, 14, 19, and vimentin in the co-cultured HPK. This in vitro finding partially correlates with pseudoepitheliomatous hyperplasia observed in melanoma biopsies. We provide evidence of FGF-2, CXCL-1, IL-8, and VEGF-A participation in the activity of melanoma cells on keratinocytes. CONCLUSION: We conclude that the MC are able to influence locally the differentiation pattern of keratinocytes in vivo as well as in vitro. This interaction further highlights the role of intercellular interactions in melanoma. The reciprocal role of activated keratinocytes on biology of melanoma cells shall be verified in the future.
- MeSH
- buněčná diferenciace * genetika MeSH
- chemokin CXCL1 farmakologie MeSH
- dospělí MeSH
- epidermis cytologie patologie MeSH
- fibroblastový růstový faktor 2 farmakologie MeSH
- interleukin-8 farmakologie MeSH
- keratin-10 metabolismus MeSH
- keratin-14 metabolismus MeSH
- keratinocyty cytologie účinky léků metabolismus MeSH
- lidé středního věku MeSH
- lidé MeSH
- melanocyty metabolismus MeSH
- melanom metabolismus patologie MeSH
- metastázy nádorů MeSH
- mezibuněčná komunikace * MeSH
- nádorové buněčné linie MeSH
- proteiny S100 metabolismus MeSH
- senioři MeSH
- stanovení celkové genové exprese MeSH
- vaskulární endoteliální růstový faktor A farmakologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
With the increasing demand for noninvasive approaches in monitoring head and neck cancer, circulating nucleic acids have been shown to be a promising tool. We focused on the global transcriptome of serum samples of head and neck squamous cell carcinoma (HNSCC) patients in comparison with healthy individuals. We compared gene expression patterns of 36 samples. Twenty-four participants including 16 HNSCC patients (from 12 patients we obtained blood samples 1 year posttreatment) and 8 control subjects were recruited. The Illumina HumanWG-6 v3 Expression BeadChip was used to profile and identify the differences in serum mRNA transcriptomes. We found 159 genes to be significantly changed (Storey's P value <0.05) between normal and cancer serum specimens regardless of factors including p53 and B-cell lymphoma family members (Bcl-2, Bcl-XL). In contrast, there was no difference in gene expression between samples obtained before and after surgery in cancer patients. We suggest that microarray analysis of serum cRNA in patients with HNSCC should be suitable for refinement of early stage diagnosis of disease that can be important for development of new personalized strategies in diagnosis and treatment of tumours but is not suitable for monitoring further development of disease.
- MeSH
- analýza hlavních komponent MeSH
- apoptóza genetika MeSH
- demografie MeSH
- dospělí MeSH
- genom lidský genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- messenger RNA krev genetika MeSH
- mikročipová analýza * MeSH
- nádorový supresorový protein p53 metabolismus MeSH
- nádory hlavy a krku krev genetika patologie MeSH
- regulace genové exprese u nádorů MeSH
- senioři MeSH
- signální transdukce genetika MeSH
- spinocelulární karcinom krev genetika patologie MeSH
- stanovení celkové genové exprese MeSH
- studie případů a kontrol MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND INFORMATION: Considering an analogy between wound healing and tumour progression, we studied chemokine and cytokine transcription and expression in normal fibroblasts by co-culture and in situ. RESULTS: Whole-genome transcriptome profiling revealed strong upregulation for the interleukin (IL)-6, IL-8 and the chemokine CXCL-1 in in vitro co-cultures of normal fibroblasts with either normal or malignant epithelial cells compared to fibroblast cultures. The same ILs/chemokines were distinctly upregulated in clinical samples of squamous cell carcinoma when compared with paired normal mucosae. Analysis of culture supernatants showed that during the course of co-culture of the fibroblasts with the epithelial cells, IL-6, IL-8 and CXCL-1 were secreted to the culture medium. Experiments with addition of any of the proteins to the culture medium supported the notion that these ILs/chemokines strongly contributed to maintenance of a low-differentiation phenotype of epithelial cells, evaluated by the detection of keratin-8. Simultaneous addition of all factors increased the extent of the effect. These studies were extended by experiments with epithelial cells, either cultured in medium conditioned by preceding use for malignant keratinocytes without and in the presence of normal or cancer-associated fibroblasts or medium containing antibodies against IL-6, IL-8 and CXCL-1. CONCLUSIONS: Our results indicate an analogy between wound healing and tumour growth, support the importance of epithelial-mesenchymal interaction in this model system and establish a potential bio-inspired anticancer therapy.
- MeSH
- chemokin CXCL1 biosyntéza genetika MeSH
- epitelo-mezenchymální tranzice genetika MeSH
- epitelové buňky metabolismus patologie MeSH
- fibroblasty metabolismus patologie MeSH
- imunohistochemie MeSH
- interleukin-6 biosyntéza genetika MeSH
- interleukin-8 biosyntéza genetika MeSH
- lidé MeSH
- nádorové buněčné linie MeSH
- nádorové proteiny biosyntéza genetika MeSH
- nádory glandulární a epitelové metabolismus patologie MeSH
- regulace genové exprese u nádorů * MeSH
- škára metabolismus patologie MeSH
- stanovení celkové genové exprese MeSH
- transkriptom genetika MeSH
- upregulace genetika MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- práce podpořená grantem MeSH
Epithelial-mesenchymal interaction between stromal fibroblasts and cancer cells influences the functional properties of tumor epithelium, including the tumor progression and spread. We compared fibroblasts prepared from stroma of squamous cell carcinoma and normal dermal fibroblasts concerning their biological activity toward normal keratinocytes assessed by immunocytochemistry and profiling of gene activation for growth factors/cytokines by microarray chip technology. IGF-2 and BMP-4 were determined as candidate factors responsible for tumor-associated fibroblast activity that influences normal epithelia. This effect was confirmed by addition of recombinant IGF-2 and BMP4, respectively, to the culture medium. This hypothesis was also verified by inhibition experiments where blocking antibodies were employed in the medium conditioned by cancer-associated fibroblast. Presence of these growth factors was also detected in tumor samples.
- MeSH
- buňky NIH 3T3 MeSH
- čipová analýza proteinů MeSH
- fenotyp MeSH
- fibroblasty metabolismus MeSH
- imunohistochemie MeSH
- insulinu podobný růstový faktor II biosyntéza MeSH
- keratinocyty cytologie metabolismus MeSH
- kostní morfogenetický protein 4 biosyntéza MeSH
- lidé MeSH
- myši MeSH
- nádory hlavy a krku metabolismus patologie MeSH
- rekombinantní proteiny biosyntéza MeSH
- spinocelulární karcinom metabolismus patologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
OBJECTIVE: Prostate cancer is now recognized as one of the principal medical problems facing male population and the commonest cancer in males in delevoped countries. The aim of this study was to find out whether serum hormone levels differ significantly in localized (pT2) and locally advanced (pT3-pT4 or N1) prostate cancer. METHODS: In 250 men (mean age+/-SEM: 63.8+/-0.4) who underwent radical retropubic prostatectomy for histologically confirmed prostate cancer were analyzed serum samples for total testosterone, dehydroepiandrosterone sulfate, estradiol, progesterone, prolactin, cortisol, sex hormone-binding globulin, luteinizing hormone and follicle stimulating hormone. Free testosterone content was calculated from total testosterone and SHBG concentrations. RESULTS: Significantly lower serum level of FSH, i.e. 5.63+/-0.31 vs. 7.07+/-0.65 U/L was found in patients with localized prostate cancer than in locally advanced (p<0.05). Significant correlation was found between serum levels of DHEAS and cortisol in both groups (p<0.02), estradiol and prolactin in patients with locally advanced prostate cancer, as well between LH and prolactin (p<0.05). No differences were found in other observed hormones. CONCLUSION: The results point to importance of hormone status as possible additional prognostic marker for patients with prostate cancer. Considerable research is needed to further understand influence of hormones on prostate cancer.
- MeSH
- estradiol krev MeSH
- financování organizované MeSH
- folikuly stimulující hormon krev MeSH
- hormony krev MeSH
- hydrokortison krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- luteinizační hormon krev MeSH
- nádory prostaty komplikace chirurgie krev MeSH
- prognóza MeSH
- progrese nemoci MeSH
- prolaktin krev MeSH
- prostatektomie MeSH
- senioři MeSH
- steryl-sulfatasa krev MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
