Crizotinib targets in glioblastoma stem cells
| Autor: | Julie Godet, Pierre Rivet, Audelaure Junca, Anais Balbous, Ulrich Cortes, Karline Guilloteau, Gaëlle Tachon, Claire Villalva, Lucie Karayan-Tapon, Michel Wager |
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| Přispěvatelé: | Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Laboratoire de Physique et Physiologie Intégratives de l’Arbre en environnement Fluctuant (PIAF), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Recherche Agronomique (INRA), Institut National de la Transfusion Sanguine [Paris] (INTS), Laboratoire Inflammation, Tissus épithéliaux et Cytokines (LITEC), Université de Poitiers, Laboratoire de neurosciences expérimentales et cliniques (LNEC), Université de Poitiers-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire Cancérologie Biologique Poitiers, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Département d'Anatomocytopathologie, Cellules souches leucémiques et thérapeuthiques, Université de Poitiers-Centre hospitalier universitaire de Poitiers (CHU Poitiers) |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine Cancer Research Pyridines [SDV]Life Sciences [q-bio] DNA Mutational Analysis Tyrosine-kinase inhibitor Central Nervous System Neoplasms 0302 clinical medicine hemic and lymphatic diseases Anaplastic Lymphoma Kinase Molecular Targeted Therapy ComputingMilieux_MISCELLANEOUS Original Research Cancer Biology glioblastoma stem cells Middle Aged Protein-Tyrosine Kinases Proto-Oncogene Proteins c-met 3. Good health Oncology 030220 oncology & carcinogenesis Neoplastic Stem Cells MET Immunohistochemistry Female Stem cell ROS1 medicine.drug endocrine system medicine.drug_class [SDV.CAN]Life Sciences [q-bio]/Cancer Biology 03 medical and health sciences Crizotinib Cell Line Tumor Proto-Oncogene Proteins medicine [SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO] Humans Radiology Nuclear Medicine and imaging glioma stem cell microarray Lung cancer Protein Kinase Inhibitors Aged Polysomy fungi Mesenchymal stem cell Receptor Protein-Tyrosine Kinases medicine.disease Molecular biology 030104 developmental biology ALK Cancer research Pyrazoles Glioblastoma |
| Zdroj: | Cancer Medicine Cancer Medicine, Wiley, 2017, 6 (11), pp.2625-2634. ⟨10.1002/cam4.1167⟩ |
| ISSN: | 2045-7634 |
| Popis: | Glioblastoma stem cells (GSCs) are believed to be involved in the mechanisms of tumor resistance, therapeutic failures, and recurrences after conventional glioblastoma therapy. Therefore, elimination of GSCs might be a prerequisite for the development of successful therapeutic strategies. ALK, ROS1, and MET are targeted by Crizotinib, a tyrosine kinase inhibitor which has been approved for treatment of ALK‐rearranged non–small‐cell lung cancer. In this study we investigated ALK, ROS1, and MET status in nine glioblastoma stem cell lines and tumors from which they arise. Fluorescent in situ hybridization (FISH), Sanger's direct sequencing, and immunohistochemistry were used to screen genomic rearrangements (or amplifications), genomic mutations, and protein expression, respectively. The immunohistochemical and FISH studies revealed no significant dysregulation of ROS1 in GSCs and associated tumors. Neither amplification nor polysomy of ALK was observed in GSC, but weak overexpression was detected by IHC in three of nine GSCs. Similarly, no MET amplification was found by FISH but three GSCs presented significant immunohistochemical staining. No ALK or MET mutation was found by Sanger's direct sequencing. In this study, we show no molecular rearrangement of ALK, ROS1, and MET that would lead us not to propose, as a valid strategy, the use of crizotinib to eradicate GSCs. However, MET was overexpressed in all GSCs with mesenchymal subtype and three GSCs presented an overexpression of ALK. Therefore, our study corroborates the idea that MET and ALK may assume a role in the tumorigenicity of GSC. |
| Databáze: | OpenAIRE |
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