Academic Journal
Identification and characterization of stromal-like cells with CD207+/low CD1a+/low phenotype derived from histiocytic lesions – a perspective in vitro model for drug testing
| العنوان: | Identification and characterization of stromal-like cells with CD207+/low CD1a+/low phenotype derived from histiocytic lesions – a perspective in vitro model for drug testing |
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| المؤلفون: | Śmieszek, Agnieszka, Marcinkowska, Klaudia, Małas, Zofia, Sikora, Mateusz, Kępska, Martyna, Nowakowska, Beata A., Deperas, Marta, Smyk, Marta, Rodriguez-Galindo, Carlos, Raciborska, Anna |
| المساهمون: | Agencja Badań Medycznych |
| المصدر: | BMC Cancer ; volume 24, issue 1 ; ISSN 1471-2407 |
| بيانات النشر: | Springer Science and Business Media LLC |
| سنة النشر: | 2024 |
| الوصف: | Background Histiocytoses are rare disorders manifested by increased proliferation of pathogenic myeloid cells sharing histological features with macrophages or dendritic cells and accumulating in various organs, i.a., bone and skin. Pre-clinical in vitro models that could be used to determine molecular pathways of the disease are limited, hence research on histiocytoses is challenging. The current study compares cytophysiological features of progenitor, stromal-like cells derived from histiocytic lesions (sl-pHCs) of three pediatric patients with different histiocytoses types and outcomes. The characterized cells may find potential applications in drug testing. Methods Molecular phenotype of the cells, i.e. expression of CD1a and CD207 (langerin), was determined using flow cytometry. Cytogenetic analysis included GTG-banded metaphases and microarray (aCGH) evaluation. Furthermore, the morphology and ultrastructure of cells were evaluated using a confocal and scanning electron microscope. The microphotographs from the confocal imaging were used to reconstruct the mitochondrial network and its morphology. Basic cytophysiological parameters, such as viability, mitochondrial activity, and proliferation, were analyzed using multiple cellular assays, including Annexin V/7-AAD staining, mitopotential analysis, BrdU test, clonogenicity analysis, and distribution of cells within the cell cycle. Biomarkers potentially associated with histiocytoses progression were determined using RT-qPCR at mRNA, miRNA and lncRNA levels. Intracellular accumulation of histiocytosis-specific proteins was detected with Western blot. Cytotoxicyty and IC50 of vemurafenib and trametinib were determined with MTS assay. Results Obtained cellular models, i.e. RAB-1, HAN-1, and CHR-1, are heterogenic in terms of molecular phenotype and morphology. The cells express CD1a/CD207 markers characteristic for dendritic cells, but also show intracellular accumulation of markers characteristic for cells of mesenchymal origin, i.e. vimentin (VIM) ... |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1186/s12885-023-11807-0 |
| DOI: | 10.1186/s12885-023-11807-0.pdf |
| DOI: | 10.1186/s12885-023-11807-0/fulltext.html |
| الاتاحة: | http://dx.doi.org/10.1186/s12885-023-11807-0 https://link.springer.com/content/pdf/10.1186/s12885-023-11807-0.pdf https://link.springer.com/article/10.1186/s12885-023-11807-0/fulltext.html |
| Rights: | https://creativecommons.org/licenses/by/4.0 ; https://creativecommons.org/licenses/by/4.0 |
| رقم الانضمام: | edsbas.B5F052E7 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1186/s12885-023-11807-0 |
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