Expression of galectin-1, galectin-3 and their glycoligands in carcinoma Dotaz Zobrazit nápovědu
The definition of biological markers for oropharynx and larynx cancer is essential to predict their clinical behavior. Since cellular glycans play an important role in biological information transfer, we have employed an endogenous lectin, galectin-3, to examine in primary squamous carcinomas, lymph node metastases, and physiological squamous epithelia whether glycans recognized by this lectin are altered in relation to the state of differentiation. The expression of galectin-3 was concomitantly evaluated by immunohistochemistry using the A1D6 monoclonal antibody. In addition, other antibodies were used for the detection of cytokeratins and desmosomal proteins (desmoplakin-1 and desmoglein). The results show the expression of galectin-3-reactive ligands in moderately/highly differentiated carcinomas only in areas exhibiting a high level of keratinization. Except for one patient out of 14, metastatic cells in lymph nodes expressed no accessible binding sites for galectin-3. No galectin-3-reactivity was detected in the basal cell layer of all studied normal epithelia (which contains the proliferating cells). The suprabasal layers were positive in epidermis and epithelium of tongue and cornea and negative in epithelium of palatine tonsil. The tumor cells expressed galectin-3 with an intensity positively correlated with tumor differentiation. The position of galectin-3-reactive sites colocalized with the two tested desmosomal proteins. However, presence of these proteins was also detected in areas of tumor and suprabasal layers of tonsil epithelium where no binding reactivity for galectin-3 was found. The present study showed that expression of galectin-3-reactive glycoligands is differentiation-dependent in normal as well as malignant squamous cells. Colocalization of galectin-3-reactive sites with desmosomal proteins (desmoplakin-1 and desmoglein) suggests an association of the galectin-3 ligand(s) with the cell surface, pointing to a potential participation of galectin-3 in mediation of intercellular contacts in these tumor types.
- MeSH
- buněčná diferenciace MeSH
- cytoskeletální proteiny metabolismus MeSH
- desmogleiny MeSH
- desmoplakiny MeSH
- diferenciační antigeny metabolismus MeSH
- epitelové buňky metabolismus MeSH
- fluorescenční barviva MeSH
- fluorescenční protilátková technika nepřímá MeSH
- galektin 3 MeSH
- keratiny metabolismus MeSH
- lidé MeSH
- ligandy MeSH
- lymfatické metastázy patologie MeSH
- membránové glykoproteiny metabolismus MeSH
- nádorové biomarkery metabolismus MeSH
- nádorové proteiny metabolismus MeSH
- nádory hlavy a krku metabolismus patologie MeSH
- prognóza MeSH
- spinocelulární karcinom metabolismus patologie MeSH
- staging nádorů metody MeSH
- vazebná místa MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- cytoskeletální proteiny MeSH
- desmogleiny MeSH
- desmoplakiny MeSH
- diferenciační antigeny MeSH
- DSP protein, human MeSH Prohlížeč
- fluorescenční barviva MeSH
- galektin 3 MeSH
- keratiny MeSH
- ligandy MeSH
- membránové glykoproteiny MeSH
- nádorové biomarkery MeSH
- nádorové proteiny MeSH
Nuclear galectins participate in splicing of pre-mRNA. In this study we detected galectins-1, -2, -3 and -7 and their glycoligands in three types of cells: fibroblasts, cancer epithelial cells and melanoma cells. The results demonstrated that the nuclear expression of distinct types of galectins and their ligands in interphasic nuclei is dependent on the cell type. The extensive binding of labelled galectins-1 and -2 to mitotic cells (around chromosomes, in mitotic spindle and in bridge connecting both daughter cells) suggests their role during the cell division.
- MeSH
- buněčné jádro metabolismus MeSH
- epitelové buňky cytologie metabolismus MeSH
- fibroblasty cytologie metabolismus MeSH
- galektin 1 MeSH
- galektiny metabolismus MeSH
- interfáze fyziologie MeSH
- lidé MeSH
- ligandy MeSH
- melanocyty cytologie metabolismus MeSH
- melanom metabolismus MeSH
- mitóza fyziologie MeSH
- molekuly buněčné adheze metabolismus MeSH
- nádorové buněčné linie MeSH
- nádory metabolismus MeSH
- růstové látky metabolismus MeSH
- spinocelulární karcinom metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- galektin 1 MeSH
- galektiny MeSH
- ligandy MeSH
- molekuly buněčné adheze MeSH
- růstové látky MeSH
UNLABELLED: The squamous stratified epithelia contain a proliferative (harboring mitotic activity) and a differentiating compartment. Due to the potential of protein-carbohydrate interactions to regulate cellular activities we introduced a mammalian lectin to cyto- and histochemical analysis. We answer the questions of whether and to what extent this new probe can pinpoint differentiation-dependent glycosylation changes in sections and in culture of keratinocytes. MATERIAL AND METHODS: Purification and labeling enabled monitoring of galectin-3 reactivity in frozen sections of human and pig epidermis and basal cell carcinomas as well as in culture of keratinocytes. The staining pattern of the lectin was correlated with the staining profile of other cell markers including desmosomal proteins, beta(1) integrin, and the proliferation marker Ki-67. The Dolichos biflorus agglutinin (DBA) sharing binding reactivity of galectin-3 to the A type histoblood group epitope was used for comparison. RESULTS: Both lectins exhibit suprabasal binding. However, their profiles were not identical, substantiated by lack of coinhibition. Strong DBA reactivity was also observed in a limited number of basal layer cells, namely in cells without the expression of the proliferation marker Ki-67. Cultured mitotic epidermal cells have no reactivity for DBA. Presence of ligands for this plant lectin was connected with decreased positivity of nuclei for Ki-67 and the occurrence of ring-shaped nucleoli, micronucleoli or absence of nucleoli. Considering colocalization the pattern of galectin-3-binding sites coincided with the presence of desmosomal proteins such as desmoplakin-1 and desmoglein but not beta(1) integrin, a potential ligand. Interestingly, studied basal cell carcinomas expressed no binding sites for galectin-3, while a limited number of cells were DBA-reactive. CONCLUSION: The expression of galectin-3-binding sites and also DBA-reactive glycoligands correlates with an increased level of differentiation and/or cessation of proliferation in the examined squamous stratified epithelia. Further application of tissue lectins for characterizing ligand expression and its modulation is an important step to reveal functional relevance.
- MeSH
- antigen Ki-67 metabolismus MeSH
- antigeny CD29 metabolismus MeSH
- bazocelulární karcinom metabolismus MeSH
- buněčná diferenciace fyziologie MeSH
- cytoskeletální proteiny metabolismus MeSH
- desmogleiny MeSH
- desmoplakiny MeSH
- epitel fyziologie MeSH
- epitelové buňky cytologie metabolismus MeSH
- galektin 3 metabolismus MeSH
- glykosylace MeSH
- imunohistochemie MeSH
- keratinocyty cytologie metabolismus MeSH
- keratiny metabolismus MeSH
- kultivované buňky MeSH
- lidé MeSH
- myši MeSH
- nádory kůže metabolismus MeSH
- prasata MeSH
- rostlinné lektiny metabolismus MeSH
- vazba proteinů MeSH
- vazebná místa MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antigen Ki-67 MeSH
- antigeny CD29 MeSH
- cytoskeletální proteiny MeSH
- desmogleiny MeSH
- desmoplakiny MeSH
- dolichos biflorus agglutinin MeSH Prohlížeč
- DSP protein, human MeSH Prohlížeč
- Dsp protein, mouse MeSH Prohlížeč
- galektin 3 MeSH
- keratiny MeSH
- rostlinné lektiny MeSH
Craniopharyngioma is a rare benign tumour originating from Rathke's pouch. This paper reports a tumour case studied with a set of markers defining protein-carbohydrate recognition. Expression of endogenous lectins and their reactive glycoligands is under differentiation-dependent control in many cell types. These parameters can be related to the degree of cell differentiation in tumours. Therefore, the expression patterns of endogenous lectins, namely galectins-1, -3, and -7, in the craniopharyngioma case were determined. Galectins-1 and -3 were also used to reveal glycoconjugates in cells and extracellular matrices, an approach that has heretofore relied largely on plant lectins. The staining pattern of craniopharyngioma is compared with that of two other types of ectodermally derived tumours, namely basal and squamous cell carcinomas. Clusters of polygonal and flattened cells with morphological characteristics of differentiated cells in the craniopharyngioma and the majority of poorly differentiated cells in squamous cell carcinomas were reactive with galectin-3. No binding of this probe was observed in cells of basal cell carcinomas and the majority of craniopharyngioma cells. In view of the lack of accessible binding in the basal layer of normal squamous epithelia where proliferative cells (including stem cells) are located, galectin-3 binding could be used to distinguish basal from suprabasal cells of squamous epithelial cells.
- MeSH
- bazocelulární nádory metabolismus patologie MeSH
- buněčná diferenciace fyziologie MeSH
- dospělí MeSH
- epitel metabolismus patologie MeSH
- epitopy MeSH
- fenotyp MeSH
- fluorescenční mikroskopie MeSH
- galektiny metabolismus MeSH
- histocytochemie MeSH
- keratiny metabolismus MeSH
- kraniofaryngeom metabolismus patologie MeSH
- lektiny MeSH
- lidé MeSH
- monoklonální protilátky MeSH
- nádorové biomarkery MeSH
- nádory hypofýzy metabolismus patologie MeSH
- polysacharidy metabolismus MeSH
- spinocelulární karcinom metabolismus patologie MeSH
- vazebná místa MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- epitopy MeSH
- galektiny MeSH
- keratiny MeSH
- lektiny MeSH
- monoklonální protilátky MeSH
- nádorové biomarkery MeSH
- polysacharidy 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
- galektin 1 metabolismus MeSH
- hojení ran fyziologie 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
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- galektin 1 MeSH
- keratiny MeSH