Galectin-7 Dotaz Zobrazit nápovědu
BACKGROUND: Galectin-7 (Gal-7) is negatively regulated in cervical cancer, and appears to be a link between the apoptotic response triggered by cancer and the anti-tumoral activity of the immune system. Our understanding of how cervical cancer cells and their molecular networks adapt in response to the expression of Gal-7 remains limited. METHODS: Meta-analysis of Gal-7 expression was conducted in three cervical cancer cohort studies and TCGA. In silico prediction and bisulfite sequencing were performed to inquire epigenetic alterations. To study the effect of Gal-7 on cervical cancer, we ectopically re-expressed it in the HeLa and SiHa cervical cancer cell lines, and analyzed their transcriptome and SILAC-based proteome. We also examined the tumor and microenvironment host cell transcriptomes after xenotransplantation into immunocompromised mice. Differences between samples were assessed with the Kruskall-Wallis, Dunn's Multiple Comparison and T tests. Kaplan-Meier and log-rank tests were used to determine overall survival. RESULTS: Gal-7 was constantly downregulated in our meta-analysis (p < 0.0001). Tumors with combined high Gal-7 and low galectin-1 expression (p = 0.0001) presented significantly better prognoses (p = 0.005). In silico and bisulfite sequencing assays showed de novo methylation in the Gal-7 promoter and first intron. Cells re-expressing Gal-7 showed a high apoptosis ratio (p < 0.05) and their xenografts displayed strong growth retardation (p < 0.001). Multiple gene modules and transcriptional regulators were modulated in response to Gal-7 reconstitution, both in cervical cancer cells and their microenvironments (FDR < 0.05 %). Most of these genes and modules were associated with tissue morphogenesis, metabolism, transport, chemokine activity, and immune response. These functional modules could exert the same effects in vitro and in vivo, even despite different compositions between HeLa and SiHa samples. CONCLUSIONS: Gal-7 re-expression affects the regulation of molecular networks in cervical cancer that are involved in diverse cancer hallmarks, such as metabolism, growth control, invasion and evasion of apoptosis. The effect of Gal-7 extends to the microenvironment, where networks involved in its configuration and in immune surveillance are particularly affected.
The human lectin galectin-7 (Gal-7; p53-induced gene-1) has anti- and pro-malignant features in different in vitro models. We tried to clarify relation of its expression to cellular and clinical parameters in head and neck squamous and basal cell carcinomas. Using a non-cross-reactive antibody, immunohistochemical staining in squamous cell epithelia (epidermis, epithelium of oropharynx and larynx) (n = 57), squamous cell carcinomas (n = 47) and lymph node metastases (n = 25), as well as basal cell carcinomas (n = 10) were studied. This monitoring was flanked by processing to assess the level of differentiation (cytokeratins 10 and 14), proliferation (Ki67) and basal lamina formation (collagen IV). The results were correlated with clinical and pathological findings (grading, TNM-staging, extracapsular spread, angio- and lymphangioinvasion, perineural invasion, recurrence and survival). Gal-7 resides in all layers of epithelia with cytoplasmic and nuclear localization in normal specimens. Basal cell carcinomas were devoid of the Gal-7 respective signal. Squamous cell carcinomas were positive, presenting different staining profiles. Intense staining was predominantly found in squamous cell cancers with high degrees of differentiation and keratinization. Fittingly, poor level of differentiation (P = 0.0009), absence of keratinization (P = 0.0105) and significant discontinuity or absence of collagen IV expression in the peritumoral basal lamina (P = 0.0024) was found in Gal-7-negative tumors. Gal-7 presence was not related to gender, primary tumor site, T-stage, N-stage, clinical stage, extracapsular spread, angio- and lymphangioinvasion, perineural spread or treatment outcome at a statistically significant level. Immunohistochemical analysis revealed a positive correlation for differentiation and keratinization to Gal-7 presence in squamous cell carcinomas. Absence of Gal-7 expression was detected in basal cell carcinomas. These clinical data delineate Gal-7 influence on differentiation in vivo, without evidence for a role in dissemination reported for lymphoma.
- MeSH
- antigen Ki-67 biosyntéza MeSH
- bazocelulární karcinom metabolismus mortalita patologie MeSH
- buněčná diferenciace MeSH
- financování organizované MeSH
- galektiny metabolismus MeSH
- imunohistochemie MeSH
- Kaplanův-Meierův odhad MeSH
- keratin-14 biosyntéza MeSH
- kolagen typu IV biosyntéza MeSH
- lidé MeSH
- nádory hlavy a krku metabolismus mortalita patologie MeSH
- spinocelulární karcinom metabolismus mortalita patologie MeSH
- staging nádorů MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- MeSH
- biologické markery MeSH
- finanční podpora výzkumu jako téma MeSH
- galektiny analýza metabolismus MeSH
- imunohistochemie metody MeSH
- karcinom diagnóza patologie MeSH
- lektiny metabolismus MeSH
- lidé MeSH
- nádory kůže patologie MeSH
- rohovka MeSH
- skvamocelulární nádory diagnóza patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- kazuistiky MeSH
PURPOSE: To assess the impact of Acanthamoeba keratitis (AK) and amniotic membrane transplantation (AMT) in corneal explants on presence of two multifunctional endogenous lectins, i.e. galectins-1 and -7. METHODS: Ten corneal explants from AK patients (five with previous AMT and five controls without this treatment) and seven specimens of disease-free control cornea were processed by indirect fluorescent immunohistochemistry. RESULTS: Immunostaining for both galectins was obtained in the epithelium, stroma and the endothelial layer of all controls, with the strongest positivity in the epithelium. Significantly decreased intensity for galectin-1 was recorded in the epithelium of corneal explants from patients with AK and AMT. The signal for galectin-7 was significantly decreased in the epithelium of AK patients and normalized after AMT. CONCLUSIONS: AMT has a marked impact on presence of the two galectins in opposite directions, encouraging complete profiling for this family of endogenous effectors.
- MeSH
- akantamébová keratitida metabolismus chirurgie MeSH
- amnion transplantace MeSH
- biologické krytí * MeSH
- biologické markery metabolismus MeSH
- dospělí MeSH
- galektin 1 MeSH
- galektiny metabolismus MeSH
- imunohistochemie MeSH
- keratoplastika perforující metody MeSH
- lidé středního věku MeSH
- lidé MeSH
- oční infekce parazitární diagnóza metabolismus chirurgie MeSH
- rohovka metabolismus chirurgie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
Following the detection of individual members of the family of galectins it is an obvious challenge to define the extent of functional overlap/divergence among these proteins. As a step to address this issue a comparative profiling has been started in the mouse as a model organism, combining sequence analysis, expression patterns and structural features in the cases of the homodimeric galectins-1, -2 and -7. Close relationship was apparent at the level of global gene organization. Scrutiny of the proximal promoter regions for putative transcription-factor-binding sites by two search algorithms uncovered qualitative and quantitative differences with potential to influence the combinatorial functionality of regulatory sequences. RT-PCR mapping with samples from an array of 17 organs revealed significant differences, separating rather ubiquitous gene expression of galectin-1 from the more restricted individual patterns of galectins-2 and -7. Using specific antisera obtained by affinity depletion including stringent controls to ascertain lack of cross-reactivity these results were corroborated at the level of galectin localization in fixed tissue sections. Nuclear presence was seen in the case of galectin-1. In addition to nonidentical expression profiles the mapping of the carbohydrate recognition domains of galectins-1 and -7 by homology modelling and docking of naturally occurring complex tetra- and pentasaccharides disclosed a series of sequence deviations which may underlie disparate affinities for cell surface glycans/glycomimetic peptides. In view of applicability the presented data can serve as useful reference to delineate changes with respect to disease and in genetically engineered models. To enable more general conclusions on the galectin network it is warranted to further pursue this combined approach within this lectin family.
- MeSH
- databáze nukleových kyselin MeSH
- dimerizace MeSH
- finanční podpora výzkumu jako téma MeSH
- galektiny genetika chemie metabolismus MeSH
- imunohistochemie MeSH
- konformace sacharidů MeSH
- ligandy MeSH
- myši MeSH
- polymerázová řetězová reakce s reverzní transkripcí MeSH
- regulace genové exprese MeSH
- sacharidy chemie MeSH
- sekvence aminokyselin MeSH
- transkripční faktory metabolismus MeSH
- vazebná místa MeSH
- výpočetní biologie MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
Keratin 19 and nuclear reactivity to an endogenous lectin, galectin-1, represent a potential marker of epidermal stem cells. We detected expression of keratin 19 and nuclear binding sites for galectin-1 in adult cells migrating from the hair follicle, where cells expressing keratin 19 are located in the bulge region. The results were compared with the expression of both markers in cells adhering from suspension prepared from the interfollicular epidermis without keratin-19-positive cells and with nuclear binding sites for galectin-1. The results were compared with data from basal cell carcinomas. All cells were analyzed concerning size, as it is known that cell diameter influences the clonogenic potential of keratinocytes. The major result of this study is the observation of transient expression of keratin 19 and nuclear galectin-1 binding sites in originally negative interfollicular epidermal cells induced by adhesion. These cells were very small in size, similar to basal cells of the interfollicular epidermis or the bulge region of the hair follicle. The influence of the suspension regimen on beta1-integrin expression, cell diameter and growth was also monitored. A population of cells highly positive for beta1 integrin of the same diameter as keratin-19-positive cells insensitive to induction of terminal differentiation by lack of anchorage was characterized. Cells of the same size were also observed in the keratin-19-positive cells of basal cell carcinomas. In conclusion, the expression of poor levels of differentiation induced by cell adhesion is transient. Also, keratin 19 expression should not be exclusively regarded as a marker of stem cell activity.
- MeSH
- antigeny CD29 analýza MeSH
- bazocelulární karcinom metabolismus patologie MeSH
- buněčná adheze MeSH
- buněčné kultury MeSH
- časové faktory MeSH
- epidermální buňky MeSH
- epidermis chemie MeSH
- financování organizované MeSH
- galektin 1 analýza MeSH
- galektin 3 analýza MeSH
- keratinocyty cytologie chemie MeSH
- keratiny analýza MeSH
- kultivované buňky MeSH
- lidé MeSH
- nádory kůže metabolismus patologie MeSH
- pohyb buněk MeSH
- proteiny intermediálních filament analýza MeSH
- vlasový folikul cytologie chemie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- srovnávací studie MeSH
Cílem studie bylo zjistit expresi galektinu-3 (gal3), cytokeratinu 19 (CK19), neural cell adhesion molecule (NCAM) a E-cadherinu (Ecad) v nádorech štítné žlázy s folikulárními rysy, se zřetelem na jejich využití v diferenciální diagnostice. Soubor tvořilo 139 případů – 87 folikulárních adenomů (FA), 26 folikulárních karcinomů (FC) a 26 případů folikulární varianty papilárního karcinomu (FVPC). Gal3 byl exprimován v 29/87 (33%) FA, v 13/26 (50%) FC a v 24/26 (92%) FVPC. CK19 byl ex- primován v 11/87 (13%) FA, v 4/26 (15%) FC a v 17/26 (65%) FVPC. Exprese NCAM byla zastižena v 60/87 (69%) FA, v 20/26 (77%) FC a v 7/26 (27%) FVPC. Ecad byl exprimován v 81/87 (93%) FA, v 22/26 (85%) FC a v 17/26 (65%) FVPC. Senzitivita a specificita pro diagnózu maligního nádoru byly u gal3 0,70 a 0,85, u CK19 0,48 a 0,97, u NCAM 0,28 a 0,47 a u Ecad 0,48 a 0,20. V expresi všech markerů byl nalezen signifikantní rozdíl (p < 0,05) mezi FVPC versus FA a FC, naopak signifikantní rozdíl me- zi FA a FC prokázán nebyl. Detekci gal3 a CK19 je možné doporučit jako pomocné kritérium v di- ferenciální diagnostice FVPC versus FA a FC.
The aim of the study was to evaluate the expression of galectin-3 (gal3), cytokeratin 19 (CK19), neural cell adhesion molecule (NCAM), and E-cadherin (Ecad) in thyroid gland tumors with follicular growth pattern with particular focus on their use in differential diagnosis. A series of 139 cases – 87 follicular adenomas (FAs), 26 follicular carcinomas (FCs), and 26 cases of the follicular variant of papillary carcinoma (FVPC) was studied. Expression of gal3 was found in 29/87 (33%) of FAs, in 13/26 (50%) of FCs, and in 24/26 (92%) of FVPCs. Expression of CK19 was found in 11/87 (13%) of FAs, in 4/26 (15%) of FCs, and in 17/26 (65%) of FVPCs. Expression of NCAM was found in 60/87 (69%) of FAs, in 20/26 (77%) of FCs, and in 7/26 (27%) FVPCs. Expression of Ecad was found in 81/87 (93%) of FAs, in 22/26 (85%) of FCs, and in 17/26 (65%) of FVPCs. The sensitivity and specificity of gal3 for malignancy were 0.70 and 0.85, of CK19 0.48 and 0.98, of NCAM 0.28 and 0.47, and of Ecad 0.48 and 0.20, respectively. A significant difference (p < 0.05) in expression of all studied markers between FVPC versus FA and FC was found, in contrast to FA and FC. Therefore, the use of gal3 and CK19 in differential diagnosis of FVPC versus FA and FC can be recommended.
- MeSH
- diferenciální diagnóza MeSH
- folikulární adenokarcinom imunologie patologie MeSH
- folikulární papilární karcinom imunologie patologie MeSH
- galektiny MeSH
- imunohistochemie metody statistika a číselné údaje využití MeSH
- kadheriny MeSH
- keratiny MeSH
- lidé MeSH
- molekula buněčné adheze nervové L1 MeSH
- nádorové biomarkery MeSH
- nádory štítné žlázy etiologie patologie MeSH
- testy funkce štítné žlázy MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- srovnávací studie MeSH
This article summarizes research using cells derived from epidermis of the miniature pigs for use as a cell therapy for skin repair and as a model for squamous carcinoma of the head and neck. Stem cells are an important "tool" for biomedical research. Adult stem cells are defined functionally, as cells that have the capacity to self-renew as well as the ability to generate differentiated cells. They are present in defined tissue microenvironments called niches. Asymmetric mitosis allows them to produce one daughter cell with the properties of stem cells (self-renewal) and a second cell with characteristics of progenitor cells, or transit amplifying cells, which proliferate quickly but with a limited number of mitotic divisions. Porcine epidermal stem cells, located in the bulge region of the outer root sheath of hair follicles, migrate in vitro from hair sheaths and because they are resistant to anoikis (detachment induced apoptosis), survive in non-adhesive conditions to form spheroids. These cells express keratins, galectin-1 and their nuclei are rich in DeltaNp63alpha. Interestingly, the multiple phenotype analysis of the human tumor cells in squamous carcinoma of head and neck revealed similarities with epidermal stem cells. These cancer stem cells are usually located on the periphery of the tumor where the invasive front of the tumor responsible for its aggressive behavior is located. In contrast, extensive expression of markers of terminal differentiation such as expression of glycoligands reactive for the endogenous lectin, galectin-3, indicates better tumor prognosis.
- MeSH
- epidermální buňky MeSH
- epidermis MeSH
- financování organizované MeSH
- galektin 1 metabolismus MeSH
- hojení ran MeSH
- keratiny metabolismus MeSH
- kmenové buňky fyziologie MeSH
- lidé MeSH
- mitóza MeSH
- nádory hlavy a krku terapie MeSH
- prasata MeSH
- transplantace kmenových buněk MeSH
- viabilita buněk MeSH
- vlasový folikul cytologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
