دورية أكاديمية
Expression and pharmacological inhibition of TrkB and EGFR in glioblastoma.
| العنوان: | Expression and pharmacological inhibition of TrkB and EGFR in glioblastoma. |
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| المؤلفون: | Pinheiro KV; Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre, RS, 90035-003, Brazil.; Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, Rua Sarmento Leite, 500 (ICBS, Campus Centro/UFRGS), Porto Alegre, RS, 90050-170, Brazil., Thomaz A; Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre, RS, 90035-003, Brazil.; Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, Rua Sarmento Leite, 500 (ICBS, Campus Centro/UFRGS), Porto Alegre, RS, 90050-170, Brazil.; Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster, LA 4YG, UK., Souza BK; Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre, RS, 90035-003, Brazil.; Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, Rua Sarmento Leite, 500 (ICBS, Campus Centro/UFRGS), Porto Alegre, RS, 90050-170, Brazil.; Children's Cancer Institute, Porto Alegre, RS, 90620-110, Brazil., Metcalfe VA; Faculty of Clinical and Biomedical Sciences, School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, Lancashire, PR1 2HE, UK., Freire NH; Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre, RS, 90035-003, Brazil., Brunetto AT; Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre, RS, 90035-003, Brazil.; Children's Cancer Institute, Porto Alegre, RS, 90620-110, Brazil., de Farias CB; Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre, RS, 90035-003, Brazil.; Children's Cancer Institute, Porto Alegre, RS, 90620-110, Brazil., Jaeger M; Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre, RS, 90035-003, Brazil.; Children's Cancer Institute, Porto Alegre, RS, 90620-110, Brazil., Bambini V; Faculty of Clinical and Biomedical Sciences, School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, Lancashire, PR1 2HE, UK., Smith CGS; Faculty of Clinical and Biomedical Sciences, School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, Lancashire, PR1 2HE, UK., Shaw L; Faculty of Clinical and Biomedical Sciences, School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, Lancashire, PR1 2HE, UK., Roesler R; Cancer and Neurobiology Laboratory, Experimental Research Center, Clinical Hospital (CPE-HCPA), Federal University of Rio Grande do Sul, Porto Alegre, RS, 90035-003, Brazil. rafaelroesler@hcpa.edu.br.; Department of Pharmacology, Institute for Basic Health Sciences, Federal University of Rio Grande do Sul, Rua Sarmento Leite, 500 (ICBS, Campus Centro/UFRGS), Porto Alegre, RS, 90050-170, Brazil. rafaelroesler@hcpa.edu.br. |
| المصدر: | Molecular biology reports [Mol Biol Rep] 2020 Sep; Vol. 47 (9), pp. 6817-6828. Date of Electronic Publication: 2020 Aug 29. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Reidel Country of Publication: Netherlands NLM ID: 0403234 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-4978 (Electronic) Linking ISSN: 03014851 NLM ISO Abbreviation: Mol Biol Rep Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Dordrecht, Boston, Reidel. |
| مواضيع طبية MeSH: | Antineoplastic Agents/*pharmacology , Brain Neoplasms/*metabolism , Enzyme Inhibitors/*pharmacology , Glioblastoma/*metabolism , Membrane Glycoproteins/*metabolism , Protein Kinase Inhibitors/*pharmacology , Receptor, trkB/*metabolism, Animals ; Azepines/pharmacology ; Benzamides/pharmacology ; Brain Neoplasms/genetics ; Cell Cycle/drug effects ; Cell Cycle/genetics ; Cell Line, Tumor ; Cell Survival/drug effects ; Cell Survival/genetics ; Drug Synergism ; ErbB Receptors/antagonists & inhibitors ; ErbB Receptors/genetics ; ErbB Receptors/metabolism ; Glioblastoma/genetics ; Humans ; Membrane Glycoproteins/antagonists & inhibitors ; Membrane Glycoproteins/genetics ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Grading ; Quinazolines/pharmacology ; Receptor, trkB/antagonists & inhibitors ; Receptor, trkB/genetics ; Tyrphostins/pharmacology ; Xenograft Model Antitumor Assays |
| مستخلص: | A member of the Trk family of neurotrophin receptors, tropomyosin receptor kinase B (TrkB, encoded by the NTRK2 gene) is an increasingly important target in various cancer types, including glioblastoma (GBM). EGFR is among the most frequently altered oncogenes in GBM, and EGFR inhibition has been tested as an experimental therapy. Functional interactions between EGFR and TrkB have been demonstrated. In the present study, we investigated the role of TrkB and EGFR, and their interactions, in GBM. Analyses of NTRK2 and EGFR gene expression from The Cancer Genome Atlas (TCGA) datasets showed an increase in NTRK2 expression in the proneural subtype of GBM, and a strong correlation between NTRK2 and EGFR expression in glioma CpG island methylator phenotype (G-CIMP+) samples. We showed that when TrkB and EGFR inhibitors were combined, the inhibitory effect on A172 human GBM cells was more pronounced than when either inhibitor was given alone. When U87MG GBM cells were xenografted into the flank of nude mice, tumor growth was delayed by treatment with TrkB and EGFR inhibitors, given alone or combined, only at specific time points. Intracranial GBM growth in mice was not significantly affected by drug treatments. Our findings indicate that correlations between NTRK2 and EGFR expression occur in specific GBM subgroups. Also, our results using cultured cells suggest for the first time the potential of combining TrkB and EGFR inhibition for the treatment of GBM. |
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| معلومات مُعتمدة: | 305647/2019-9 National Council for Scientific and Technological Development (CNPq); 409287/2016-4 National Council for Scientific and Technological Development (CNPq) |
| فهرسة مساهمة: | Keywords: Brain tumor; Epidermal growth factor receptor; Glioblastoma; Growth factor receptor; Neurotrophin; Tropomyosin receptor kinase B |
| المشرفين على المادة: | 0 (ANA 12 compound) 0 (Antineoplastic Agents) 0 (Azepines) 0 (Benzamides) 0 (Enzyme Inhibitors) 0 (Membrane Glycoproteins) 0 (Protein Kinase Inhibitors) 0 (Quinazolines) 0 (Tyrphostins) 170449-18-0 (RTKI cpd) EC 2.7.10.1 (EGFR protein, human) EC 2.7.10.1 (ErbB Receptors) EC 2.7.10.1 (Receptor, trkB) EC 2.7.10.1 (tropomyosin-related kinase-B, human) |
| تواريخ الأحداث: | Date Created: 20200831 Date Completed: 20210603 Latest Revision: 20210603 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1007/s11033-020-05739-2 |
| PMID: | 32862352 |
| قاعدة البيانات: | MEDLINE |
Find this article in full text from Springer Verlag. 
Full Text Finder | تدمد: | 1573-4978 |
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| DOI: | 10.1007/s11033-020-05739-2 |