In vitro and in vivo discrepancy in inducing apoptosis by mesenchymal stromal cells delivering membrane-bound tumor necrosis factor-related apoptosis inducing ligand in osteosarcoma pre-clinical models
| العنوان: | In vitro and in vivo discrepancy in inducing apoptosis by mesenchymal stromal cells delivering membrane-bound tumor necrosis factor-related apoptosis inducing ligand in osteosarcoma pre-clinical models |
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| المؤلفون: | Romain Guiho, Régis Brion, Dominique Heymann, Sarah Renault, Mathias Chatelais, Massimo Dominici, Giulia Grisendi, Françoise Rédini, Kevin Biteau, Julien Taurelle |
| المساهمون: | maurice, sandrine, Sarcomes osseux et remodelage des tissus calcifiés - Phy-Os [Nantes - INSERM U1238] (Phy-Os), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bretagne Loire (UBL)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Birth Defects Research Centre [London, UK] (Developmental Biology and Cancer Programme), University College of London [London] (UCL)-UCL Great Ormond Street Institute of Child Health [London, UK], Department of Medical and Surgical Sciences for Children and Adults [Modena, Italy] (Laboratory of Cellular Therapy), Università degli Studi di Modena e Reggio Emilia = University of Modena and Reggio Emilia (UNIMORE), Department of Oncology and Metabolism [Sheffield, UK] (INSERM European Associated Laboratory 'Sarcoma Research Unit'), The University of Sheffield [Sheffield, U.K.], Hétérogénéité Tumorale et Médecine de Précision [Saint-Herblain] (Site René Gauducheau), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER-UNICANCER, Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), This study received funding from la Ligue Contre le Cancer. In addition, this project was carried out with thanks to the support of the Fédération Enfants et Santé and the Société Française de Lutte Contre les Cancers et les Leucémies de L'enfant et de L'adolescent. This project was conducted with financial support from the association Étoile de Martin (R.G.).This work was supported in part by the following: the Associazione Italiana Ricerca Cancro (AIRC) IG 2012 Grant number 12755 (M.D.), the Ministero Italiano Istruzione Università e Ricerca PRIN 2008WECX78 (M.D.), the Ministero della Salute Bando GR-2008-1145964 (MD), and the Associazione ASEOP (M.D. and G.G.)., Università degli Studi di Modena e Reggio Emilia (UNIMORE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA) |
| المصدر: | Cytotherapy Cytotherapy, 2018, Epub ahead of print. ⟨10.1016/j.jcyt.2018.06.013⟩ Cytotherapy, Elsevier, 2018, Epub ahead of print. ⟨10.1016/j.jcyt.2018.06.013⟩ |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | 0301 basic medicine, Tumor necrosis factor (TNF)-Related Apoptosis Inducing Ligand, Cancer Research, medicine.medical_treatment, Apoptosis, TNF-Related Apoptosis-Inducing Ligand, Mice, 0302 clinical medicine, Immunology and Allergy, Genetics (clinical), Cells, Cultured, Osteosarcoma, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Transfection, Adoptive Transfer, 3. Good health, Tumor necrosis factor (TNF)–Related Apoptosis Inducing Ligand, Cytokine, Oncology, 030220 oncology & carcinogenesis, mesenchymal stromal cells, osteosarcoma, Immunology, Cell Biology, Transplantation, Tumor necrosis factor alpha, Mice, Nude, [SDV.CAN]Life Sciences [q-bio]/Cancer, Bone Neoplasms, In Vitro Techniques, Mesenchymal Stem Cell Transplantation, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, Animals, Humans, business.industry, Mesenchymal stem cell, Mesenchymal Stem Cells, Genetic Therapy, medicine.disease, Xenograft Model Antitumor Assays, 030104 developmental biology, Tumor progression, Cell culture, Cancer research, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology |
| الوصف: | International audience; In vitro and in vivo discrepancy in inducing apoptosis by mesenchymal stromal cells delivering membrane-bound tumor necrosis factorÀrelated apoptosis inducing ligand in osteosarcoma pre-clinical models Abstract Background: Osteosarcoma (OS) is the most frequent pediatric malignant bone tumor. OS patients have not seen any major therapeutic progress in the last 30 years, in particular in the case of metastatic disease, which requires new therapeutic strategies. The pro-apoptotic cytokine Tumor necrosis factor (TNF)ÀRelated Apoptosis Inducing Ligand (TRAIL) can selectively kill tumor cells while sparing normal cells, making it a promising therapeutic tool in several types of cancer. However, many OS cell lines appear resistant to recombinant human (rh)TRAIL-induced apoptosis. We, therefore, hypothesized that TRAIL presentation at the membrane level of carrier cells might overcome this resistance and trigger apoptosis. Methods: To address this, human adipose mesenchymal stromal cells (MSCs) transfected in a stable manner to express membrane-bound full-length human TRAIL (mbTRAIL) were co-cultured with several human OS cell lines. Results: This induced apoptosis by cell-to-cell contact even in cell lines initially resistant to rhTRAIL. In contrast, mbTRAIL delivered by MSCs was not able to counteract tumor progression in this OS orthotopic model. Discussion: This was partly due to the fact that MSCs showed a potential to support tumor development. Moreover, the expression of mbTRAIL did not show caspase activation in adjacent tumor cells. |
| وصف الملف: | application/pdf |
| تدمد: | 1477-2566 1465-3249 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::e23de5aaea44d2cbf2bb109b5a79e928Test https://pubmed.ncbi.nlm.nih.gov/30093324Test |
| حقوق: | EMBARGO |
| رقم الانضمام: | edsair.doi.dedup.....e23de5aaea44d2cbf2bb109b5a79e928 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14772566 14653249 |
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