The identification of cancer stem cell markers represents one of the very relevant research topics because cancer stem cells play important roles in tumour initiation and progression, as well as during metastasis formation and in relapse of the disease. This article summarises recent knowledge on well-known and putative cancer stem cell markers in various types of bone and soft-tissue sarcomas. Special attention is paid to the detection of CD133, ABC transporters, nestin and aldehyde dehydrogenase that have been intensively studied both in tumour tissues and in sarcoma cell lines during the past few years. Finally, an overview is given of the possible CSC phenotypes provided by functional assays of tumourigenicity.
- MeSH
- ABC transportéry analýza MeSH
- aldehyddehydrogenasa analýza MeSH
- antigen AC133 MeSH
- CD antigeny analýza MeSH
- glykoproteiny analýza MeSH
- lidé MeSH
- nádorové biomarkery analýza MeSH
- nádorové kmenové buňky metabolismus MeSH
- nestin MeSH
- peptidy analýza MeSH
- proteiny intermediálních filament analýza MeSH
- proteiny nervové tkáně analýza MeSH
- sarkom diagnóza metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
- Názvy látek
- ABC transportéry MeSH
- aldehyddehydrogenasa MeSH
- antigen AC133 MeSH
- CD antigeny MeSH
- glykoproteiny MeSH
- nádorové biomarkery MeSH
- NES protein, human MeSH Prohlížeč
- nestin MeSH
- peptidy MeSH
- PROM1 protein, human MeSH Prohlížeč
- proteiny intermediálních filament MeSH
- proteiny nervové tkáně MeSH
PURPOSE: To detect and isolate cells with stem cell (SC) characteristics in the limbus of the mouse. METHODS: Limbal tissues from BALB/c mice were trypsin-dissociated and separated on the gradient Percoll (Fluka, Buchs, Switzerland). Several fractions were isolated and characterized by real-time PCR for the presence of limbal SC markers and differentiation markers of corneal epithelial cells by flow cytometry for the determination of the side-population (SP) phenotype and growth properties in vitro. RESULTS: Cells retained in the lightest fraction (40% Percoll) and in the densest fraction (80% Percoll) of the gradient were both enriched for populations with a high expression of the SC markers ABCG2 and Lgr5 and also expressing the SP phenotype. However, the lightest fraction (representing approximately 12% of total limbal cells) contained cells with the strongest spontaneous proliferative capacity and expressed the corneal epithelial differentiation marker K12. In contrast the densest fraction (<7% of original cells) was K12 negative and contained small nonspontaneously proliferating cells, which instead were positive for p63. Unexpectedly, cells from this fraction had the highest proliferative activity when cultured on a 3T3 feeder cell monolayer. CONCLUSIONS: These findings demonstrate the presence of two distinct populations of corneal epithelial cells with limbal SC characteristics, based on differential expression of the keratin-specific marker K12 and transcription factor p63, and suggest a difference in developmental stage of the two populations, with the K12(-)p63(+) population being closer to the primitive limbal SC.
- MeSH
- ABC transportér z rodiny G, člen 2 MeSH
- ABC transportéry analýza genetika MeSH
- buněčné dělení MeSH
- buňky 3T3 MeSH
- centrifugace - gradient hustoty metody MeSH
- fibroblasty cytologie MeSH
- kmenové buňky cytologie fyziologie MeSH
- myši inbrední BALB C MeSH
- myši MeSH
- oxid křemičitý MeSH
- polymerázová řetězová reakce MeSH
- povidon MeSH
- průtoková cytometrie MeSH
- rohovkový epitel cytologie MeSH
- separace buněk metody MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- ABC transportér z rodiny G, člen 2 MeSH
- ABC transportéry MeSH
- Abcg2 protein, mouse MeSH Prohlížeč
- oxid křemičitý MeSH
- Percoll MeSH Prohlížeč
- povidon MeSH
Breast cancer resistance protein (BCRP/ABCG2) is a member of the ATP-binding cassette transporter family that recognizes a variety of chemically unrelated compounds. Its expression has been revealed in many mammal tissues, including placenta. The purpose of this study was to describe its role in transplacental pharmacokinetics using rat placental HRP-1 cell line and dually perfused rat placenta. In HRP-1 cells, expression of Bcrp, but not P-glycoprotein, was revealed at mRNA and protein levels. Cell accumulation studies confirmed Bcrp-dependent uptake of BODIPY FL prazosin. In the placental perfusion studies, a pharmacokinetic model was applied to distinguish between passive and Bcrp-mediated transplacental passage of cimetidine as a model substrate. Bcrp was shown to act in a concentration-dependent manner and to hinder maternal-to-fetal transport of the drug. Fetal-to-maternal clearance of cimetidine was found to be 25 times higher than that in the opposite direction; this asymmetry was partly eliminated by BCRP inhibitors fumitremorgin C (2 microM) or N-(4-[2-(1,2,3,4-tetrahydro-6,7-dimethoxy-2-isoquinolinyl)ethyl]-phenyl)-9,10-dihydro-5-methoxy-9-oxo-4-acridine carboxamide (GF120918; 2 microM) and abolished at high cimetidine concentrations (1000 microM). When fetal perfusate was recirculated, Bcrp was found to actively remove cimetidine from the fetal compartment to the maternal compartment even against a concentration gradient and to establish a 2-fold maternal-to-fetal concentration ratio. Based on our results, we propose a two-level defensive role of Bcrp in the rat placenta in which the transporter 1) reduces passage of its substrates from mother to fetus but also 2) removes the drug already present in the fetal circulation.
- MeSH
- ABC transportér z rodiny G, člen 2 MeSH
- ABC transportéry analýza genetika fyziologie MeSH
- buněčné linie MeSH
- cimetidin farmakokinetika MeSH
- imunohistochemie MeSH
- krysa rodu Rattus MeSH
- messenger RNA analýza MeSH
- metabolická clearance MeSH
- P-glykoprotein fyziologie MeSH
- perfuze MeSH
- placenta metabolismus MeSH
- potkani Wistar MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- ABC transportér z rodiny G, člen 2 MeSH
- ABC transportéry MeSH
- Abcg2 protein, rat MeSH Prohlížeč
- cimetidin MeSH
- messenger RNA MeSH
- P-glykoprotein MeSH
