دورية أكاديمية
Expression and pharmacological inhibition of TrkB and EGFR in glioblastoma.
العنوان: | Expression and pharmacological inhibition of TrkB and EGFR in glioblastoma. |
---|---|
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. |
References: | Mitsudomi T, Yatabe Y (2010) Epidermal growth factor receptor in relation to tumor development: EGFR gene and cancer. FEBS J 277(2):301–308. (PMID: 19922469) Arteaga CL, Engelman JA (2014) ERBB receptors: from oncogene discovery to basic science to mechanism-based cancer therapeutics. Cancer Cell 25(3):282–303. (PMID: 246510114018830) Brennan CW, Verhaak RG, McKenna A, Campos B, Noushmehr H, Salama SR, Zheng S, Chakravarty D, Sanborn JZ, Berman SH, Beroukhim R, Bernard B, Wu CJ, Genovese G, Shmulevich I, Barnholtz-Sloan J, Zou L, Vegesna R, Shukla SA, Ciriello G, Yung WK, Zhang W, Sougnez C, Mikkelsen T, Aldape K, Bigner DD, Van Meir EG, Prados M, Sloan A, Black KL, Eschbacher J, Finocchiaro G, Friedman W, Andrews DW, Guha A, Iacocca M, O’Neill BP, Foltz G, Myers J, Weisenberger DJ, Penny R, Kucherlapati R, Perou CM, Hayes DN, Gibbs R, Marra M, Mills GB, Lander E, Spellman P, Wilson R, Sander C, Weinstein J, Meyerson M, Gabriel S, Laird PW, Haussler D, Getz G, Chin L, TCGA Research Network (2013) The somatic genomic landscape of glioblastoma. Cell 155(2):462–477. Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, Curschmann J, Janzer RC, Ludwin SK, Gorlia T, Allgeier A, Lacombe D, Cairncross JG, Eisenhauer E, Mirimanoff RO, European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups, National Cancer Institute of Canada Clinical Trials Group (2005) Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 352(10):987–996. Wen PY, Kesari S (2008) Malignant gliomas in adults. N Engl J Med 359(5):492–507. van den Bent MJ, Brandes AA, Rampling R, Kouwenhoven MC, Kros JM, Carpentier AF, Clement PM, Frenay M, Campone M, Baurain JF, Armand JP, Taphoorn MJ, Tosoni A, Kletzl H, Klughammer B, Lacombe D, Gorlia T (2009) Randomized phase II trial of erlotinib versus temozolomide or carmustine in recurrent glioblastoma: EORTC brain tumor group study 26034. J Clin Oncol 27(8):1268–1274. (PMID: 192042072667826) Vivanco I, Robins HI, Rohle D, Campos C, Grommes C, Nghiemphu PL, Kubek S, Oldrini B, Chheda MG, Yannuzzi N, Tao H, Zhu S, Iwanami A, Kuga D, Dang J, Pedraza A, Brennan CW, Heguy A, Liau LM, Lieberman F, Yung WK, Gilbert MR, Reardon DA, Drappatz J, Wen PY, Lamborn KR, Chang SM, Prados MD, Fine HA, Horvath S, Wu N, Lassman AB, DeAngelis LM, Yong WH, Kuhn JG, Mischel PS, Mehta MP, Cloughesy TF, Mellinghoff IK (2012) Differential sensitivity of glioma- versus lung cancer-specific EGFR mutations to EGFR kinase inhibitors. Cancer Discov 2(5):458–471. (PMID: 225888833354723) Keller S, Schmidt MHH (2017) EGFR and EGFRvIII promote angiogenesis and cell invasion in glioblastoma: combination therapies for an effective treatment. Int J Mol Sci 18(6):E129. Roesler R, Brunetto AT, Abujamra AL, de Farias CB, Brunetto AL, Schwartsmann G (2010) Current and emerging molecular targets in glioma. Expert Rev Anticancer Ther 10(11):1735–1751. (PMID: 21080801) Park H, Poo MM (2013) Neurotrophin regulation of neural circuit development and function. Nat Rev Neurosci 14(1):7–23. Thiele CJ, Li Z, McKee AE (2009) On Trk–the TrkB signal transduction pathway is an increasingly important target in cancer biology. Clin Cancer Res 15(19):5962–5967. (PMID: 197553852756331) de Farias CB, Heinen TE, dos Santos RP, Abujamra AL, Schwartsmann G, Roesler R (2012) BDNF/TrkB signaling protects HT-29 human colon cancer cells from EGFR inhibition. Biochem Biophys Res Commun 425(2):328–332. (PMID: 22842573) Lawn S, Krishna N, Pisklakova A, Qu X, Fenstermacher DA, Fournier M, Vrionis FD, Tran N, Chan JA, Kenchappa RS, Forsyth PA (2015) Neurotrophin signaling via TrkB and TrkC receptors promotes the growth of brain tumor-initiating cells. J Biol Chem 290(6):3814–3824. (PMID: 25538243) Pinheiro KV, Alves C, Buendia M, Gil MS, Thomaz A, Schwartsmann G, de Farias CB, Roesler R (2017) Targeting tyrosine receptor kinase B in gliomas. Neuro Oncol 19(1):138–139. (PMID: 27630272) Wang X, Prager BC, Wu Q, Kim LJY, Gimple RC, Shi Y, Yang K, Morton AR, Zhou W, Zhu Z, Obara EAA, Miller TE, Song A, Lai S, Hubert CG, Jin X, Huang Z, Fang X, Dixit D, Tao W, Zhai K, Chen C, Dong Z, Zhang G, Dombrowski SM, Hamerlik P, Mack SC, Bao S, Rich JN (2018) Reciprocal signaling between glioblastoma stem cells and differentiated tumor cells promotes malignant progression. Cell Stem Cell 22(4):514–528.e5. (PMID: 296250675947947) Cocco E, Scaltriti M, Drilon A (2018) NTRK fusion-positive cancers and TRK inhibitor therapy. Nat Rev Clin Oncol 15(12):731–747. (PMID: 303335166419506) Drilon A, Laetsch TW, Kummar S, DuBois SG, Lassen UN, Demetri GD, Nathenson M, Doebele RC, Farago AF, Pappo AS, Turpin B, Dowlati A, Brose MS, Mascarenhas L, Federman N, Berlin J, El-Deiry WS, Baik C, Deeken J, Boni V, Nagasubramanian R, Taylor M, Rudzinski ER, Meric-Bernstam F, Sohal DPS, Ma PC, Raez LE, Hechtman JF, Benayed R, Ladanyi M, Tuch BB, Ebata K, Cruickshank S, Ku NC, Cox MC, Hawkins DS, Hong DS, Hyman DM (2018) Efficacy of larotrectinib in TRK fusion-positive cancers in adults and children. N Engl J Med 378(8):731–739. (PMID: 294661565857389) Jones KA, Bossler AD, Bellizzi AM, Snow AN (2019) BCR-NTRK2 fusion in a low-grade glioma with distinctive morphology and unexpected aggressive behavior. Cold Spring Harb Mol Case Stud 5(2):a003855. (PMID: 309361986549568) Thomaz A, Jaeger M, Buendia M, Bambini-Junior V, Gregianin LJ, Brunetto AL, Brunetto AT, de Farias CB, Roesler R (2016) BDNF/TrkB signaling as a potential novel target in pediatric brain tumors: anticancer activity of selective TrkB inhibition in medulloblastoma cells. J Mol Neurosci 59(3):326–333. (PMID: 26614346) Ellis AG, Doherty MM, Walker F, Weinstock J, Nerrie M, Vitali A, Murphy R, Johns TG, Scott AM, Levitzki A, McLachlan G, Webster LK, Burgess AW, Nice EC (2006) Preclinical analysis of the analinoquinazoline AG1478, a specific small molecule inhibitor of EGF receptor tyrosine kinase. Biochem Pharmacol 71(10):1422–1434. (PMID: 16522318) Cazorla M, Prémont J, Mann A, Girard N, Kellendonk C, Rognan D (2011) Identification of a low-molecular weight TrkB antagonist with anxiolytic and antidepressant activity in mice. J Clin Invest 121(5):1846–1857. (PMID: 215052633083767) Yu Y, Zhang M, Zhang X, Cai Q, Hong S, Jiang W, Xu C (2014) Synergistic effects of combined platelet-activating factor receptor and epidermal growth factor receptor targeting in ovarian cancer cells. J Hematol Oncol 7:39. (PMID: 248866784028110) Li W, Fang Q, Zhong P, Chen L, Wang L, Zhang Y, Wang J, Li X, Wang Y, Wang J, Liang G (2016) EGFR inhibition blocks palmitic acid-induced inflammation in cardiomyocytes and prevents hyperlipidemia-induced cardiac injury in mice. Sci Rep 6:24580. (PMID: 270872795263857) Thomaz A, Pinheiro KV, Souza BK, Gregianin L, Brunetto AL, Brunetto AT, de Farias CB, Jaeger MDC, Ramaswamy V, Nör C, Taylor MD, Roesler R (2019) Antitumor activities and cellular changes induced by TrkB inhibition in medulloblastoma. Front Pharmacol 10:698. (PMID: 312970576606946) Nagane M, Narita Y, Mishima K, Levitzki A, Burgess AW, Cavenee WK, Huang HJ (2001) Human glioblastoma xenografts overexpressing a tumor-specific mutant epidermal growth factor receptor sensitized to cisplatin by the AG1478 tyrosine kinase inhibitor. J Neurosurg 95:472–479. (PMID: 11565870) Chou TC, Talalay P (1984) Quantitative analysis of dose-effect relationships: the combined effects of multiple drugs or enzyme inhibitors. Adv Enzym Regul 22:27–55. Li J, Taich ZJ, Goyal A, Gonda D, Akers J, Adhikari B, Patel K, Vandenberg S, Yan W, Bao Z, Carter BS, Wang R, Mao Y, Jiang T, Chen CC (2014) Epigenetic suppression of EGFR signaling in G-CIMP+ glioblastomas. Oncotarget 5(17):7342–7356. (PMID: 252771774202127) Roesler R, de Farias CB, Abujamra AL, Brunetto AL, Schwartsmann G (2011) BDNF/TrkB signaling as an anti-tumor target. Expert Rev Anticancer Ther 11(10):1473–1475. (PMID: 21999118) Wu S, Gao F, Zheng S, Zhang C, Martinez-Ledesma E, Ezhilarasan R, Ding J, Li X, Feng N, Multani A, Sulman EP, Verhaak RG, de Groot JF, Heffernan TP, Yung WKA, Koul D (2020) EGFR amplification induces increased DNA damage response and renders selective sensitivity to Talazoparib (PARP inhibitor) in glioblastoma. Clin Cancer Res 26(6):1395–1407. (PMID: 31852834) Ciesielski MJ, Fenstermaker RA (2000) Oncogenic epidermal growth factor receptor mutants with tandem duplication: gene structure and effects on receptor function. Oncogene 19(6):810–820. (PMID: 10698499) Carrasco-García E, Saceda M, Grasso S, Rocamora-Reverte L, Conde M, Gómez-Martínez A, García-Morales P, Ferragut JA, Martínez-Lacaci I (2011) Small tyrosine kinase inhibitors interrupt EGFR signaling by interacting with erbB3 and erbB4 in glioblastoma cell lines. Exp Cell Res 317(10):1476–1489. (PMID: 21439954) Schmidt AL, de Farias CB, Abujamra AL, Kapczinski F, Schwartsmann G, Brunetto AL, Roesler R (2010) BDNF and PDE4, but not the GRPR, regulate viability of human medulloblastoma cells. J Mol Neurosci 40:303–310. (PMID: 19642024) Nör C, de Farias CB, Abujamra AL, Schwartsmann G, Brunetto AL, Roesler R (2011) The histone deacetylase inhibitor sodium butyrate in combination with brain-derived neurotrophic factor reduces the viability of DAOY human medulloblastoma cells. Childs Nerv Syst 27:897–901. (PMID: 21560052) Radin DP, Patel P (2017) BDNF: an oncogene or tumor suppressor? Anticancer Res 37(8):3983–3990. (PMID: 28739680) de Almeida Sassi F, Lunardi Brunetto A, Schwartsmann G, Roesler R, Abujamra AL (2012) Glioma revisited: from neurogenesis and cancer stem cells to the epigenetic regulation of the niche. J Oncol 2012:537861. Perus LJM, Walsh LA (2019) Microenvironmental heterogeneity in brain malignancies. Front Immunol 10:2294. (PMID: 316323936779728) Simon T, Jackson E, Giamas G (2020) Breaking through the glioblastoma micro-environment via extracellular vesicles. Oncogene 39:4477–4490. (PMID: 323669097269906) Pinet S, Bessette B, Vedrenne N, Lacroix A, Richard L, Jauberteau MO, Battu S, Lalloué F (2016) TrkB-containing exosomes promote the transfer of glioblastoma aggressiveness to YKL-40-inactivated glioblastoma cells. Oncotarget 7(31):50349–50364. (PMID: 273850985226587) Parker JJ, Dionne KR, Massarwa R, Klaassen M, Foreman NK, Niswander L, Canoll P, Kleinschmidt-Demasters BK, Waziri A (2013) Gefitinib selectively inhibits tumor cell migration in EGFR-amplified human glioblastoma. Neuro Oncol 15(8):1048–1057. (PMID: 237497853714155) Zahonero C, Aguilera P, Ramírez-Castillejo C, Pajares M, Bolós MV, Cantero D, Perez-Nuñez A, Hernández-Laín A, Sánchez-Gómez P, Sepúlveda JM (2015) Preclinical test of dacomitinib, an irreversible EGFR inhibitor, confirms its effectiveness for glioblastoma. Mol Cancer Ther 14(7):1548–1558. (PMID: 25939761) Buendia Duque M, Pinheiro KV, Thomaz A, da Silva CA, Freire NH, Brunetto AT, Schwartsmann G, Jaeger M, de Farias CB, Roesler R (2019) Combined inhibition of HDAC and EGFR reduces viability and proliferation and enhances STAT3 mRNA expression in glioblastoma cells. J Mol Neurosci 68(1):49–57. (PMID: 30887411) Sepúlveda-Sánchez JM, Vaz M, Balañá C, Gil-Gil M, Reynés G, Gallego Ó, Martínez-García M, Vicente E, Quindós M, Luque R, Ramos A, Ruano Y, Pérez-Segura P, Benavides M, Sánchez-Gómez P, Hernández-Laín A (2017) Phase II trial of dacomitinib, a pan-human EGFR tyrosine kinase inhibitor, in recurrent glioblastoma patients with EGFR amplification. Neuro Oncol 19(11):1522–1531. (PMID: 285754645737732) Makhlin I, Salinas RD, Zhang D, Jacob F, Ming GL, Song H, Saxena D, Dorsey JF, Nasrallah MP, Morrissette JJ, Binder ZA, O’Rourke DM, Desai AS, Brem S, Bagley SJ (2019) Clinical activity of the EGFR tyrosine kinase inhibitor osimertinib in EGFR-mutant glioblastoma. CNS Oncol 8(3):CNS43. (PMID: 317697266880297) |
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 |
كن أول من يترك تعليقا!