کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8451458 | 1547695 | 2018 | 41 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
In vitro and in vivo characterization of stem-like cells from canine osteosarcoma and assessment of drug sensitivity
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کلمات کلیدی
CFECXCR4DAPICXCL12Oct4Sox2CSCsCD117bFGFTumorigenicityEGFC-X-C motif chemokine receptor 4C-X-C motif chemokine ligand 12POU class 5 homeobox 1STAT3(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) - (3- (4،5-dimethylthiazol-2-yl) -2،5-diphenyltetrazolium bromide)4,6-diamidino-2-phenylindole dihydrochloride - 4،6-دیامیدینو-2-فنیلینول دی هیدروکلرایدH&E - H & EMTT - MTTOsteosarcoma - استئوسارکوماOsa - بخشSelf-renewal - خود نوسازیhematoxylin and eosin staining - رنگ آمیزی هماتوکسیلین و ائوزینcancer stem cell - سلولهای بنیادی سرطانیCancer stem cells - سلولهای بنیادی سرطانیepidermal growth factor - عامل رشد اپیدرمیbasic fibroblast growth factor - فاکتور رشد فیبروبلاست پایهsignal transducer and activator of transcription 3 - مبدل سیگنال و فعال کننده رونویسی 3Metformin - متفورمین
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
تحقیقات سرطان
پیش نمایش صفحه اول مقاله

چکیده انگلیسی
Cancer stem cell (CSC) self-renewing and drug resistance cause treatment failure and tumor recurrence. Osteosarcoma is an aggressive bone tumor characterized by biological and molecular heterogeneity, possibly dependent on CSCs. CSC identification in osteosarcoma and their efficient targeting are still open questions. Spontaneous canine osteosarcoma shares clinical and biological features with the human tumors, representing a model for translational studies. We characterized three CSC-enriched canine osteosarcoma cultures. In serum-free conditions, these CSC cultures grow as anchorage-independent spheroids, show mesenchymal-like properties and in vivo tumorigenicity, recapitulating the heterogeneity of the original osteosarcoma. Osteosarcoma CSCs express stem-related factors (Sox2, Oct4, CD133) and chemokine receptors and ligands (CXCR4, CXCL12) involved in tumor proliferation and self-renewal. Standard drugs for osteosarcoma treatment (doxorubicin and cisplatin) affected CSC-enriched and parental primary cultures, showing different efficacy within tumors. Moreover, metformin, a type-2 diabetes drug, significantly inhibits osteosarcoma CSC viability, migration and self-renewal and, in co-treatment with doxorubicin and cisplatin, enhances drug cytotoxicity. Collectively, we demonstrate that canine osteosarcoma primary cultures contain CSCs exhibiting distinctive sensitivity to anticancer agents, as a reliable experimental model to assay drug efficacy. We also provide proof-of-principle of metformin efficacy, alone or in combination, as pharmacological strategy to target osteosarcoma CSCs.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Experimental Cell Research - Volume 363, Issue 1, 1 February 2018, Pages 48-64
Journal: Experimental Cell Research - Volume 363, Issue 1, 1 February 2018, Pages 48-64
نویسندگان
Monica Gatti, Agnese Solari, Alessandra Pattarozzi, Chiara Campanella, Stefano Thellung, Lorella Maniscalco, Raffaella De Maria, Roberto Würth, Alessandro Corsaro, Adriana Bajetto, Alessandra Ratto, Angelo Ferrari, Antonio Daga, Federica Barbieri,