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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

TrkB-Targeted Therapy for Mucoepidermoid Carcinoma

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Author(s):
Wagner, Vivian P. [1, 2] ; Martins, Manoela D. [1, 3] ; Amoura, Esra [2] ; Zanella, Virgilio G. [3, 4] ; Roesler, Rafael [5, 6] ; de Farias, Caroline B. [5, 6, 7] ; Bingle, Colin D. [8] ; Vargas, Pablo A. [1] ; Bingle, Lynne [2]
Total Authors: 9
Affiliation:
[1] Univ Estadual Campinas, Piracicaba Dent Sch, Dept Oral Diag, BR-13414903 Piracicaba - Brazil
[2] Univ Sheffield, Dept Clin Dent, Oral & Maxillofacial Pathol, Sheffield S10 2TA, S Yorkshire - England
[3] Univ Fed Rio Grande do Sul, Sch Dent, Dept Pathol, BR-90035003 Porto Alegre, RS - Brazil
[4] Santa Rita Hosp, Santa Casa Misericordia Porto Alegre, Head & Neck Surg Dept, BR-90020090 Porto Alegre, RS - Brazil
[5] Univ Fed Rio Grande do Sul, Porto Alegre Clin Hosp, Expt Res Ctr, Canc & Neurobiol Lab, BR-90035903 Porto Alegre, RS - Brazil
[6] Univ Fed Rio Grande do Sul, Inst Basic Hlth Sci, Dept Pharmacol, BR-90050170 Porto Alegre, RS - Brazil
[7] Childrens Canc Inst, Rafael Koff Acordi Res Ctr, BR-90620110 Porto Alegre, RS - Brazil
[8] Univ Sheffield, Dept Infect Immun & Cardiovasc Dis, Acad Unit Resp Med, Sheffield S10 2RX, S Yorkshire - England
Total Affiliations: 8
Document type: Journal article
Source: BIOMEDICINES; v. 8, n. 12 DEC 2020.
Web of Science Citations: 0
Abstract

The brain-derived neurotrophic factor (BDNF)/tyrosine receptor kinase B (TrkB) pathway was previously associated with key oncogenic outcomes in a number of adenocarcinomas. The aim of our study was to determine the role of this pathway in mucoepidermoid carcinoma (MEC). Three MEC cell lines (UM-HMC-2, H253 and H292) were exposed to Cisplatin, the TrkB inhibitor, ANA-12 and a combination of these drugs. Ultrastructural changes were assessed through transmission electron microscopy; scratch and Transwell assays were used to assess migration and invasion; and a clonogenic assay and spheroid-forming assay allowed assessment of survival and percentage of cancer stem cells (CSC). Changes in cell ultrastructure demonstrated Cisplatin cytotoxicity, while the effects of ANA-12 were less pronounced. Both drugs, used individually and in combination, delayed MEC cell migration, invasion and survival. ANA-12 significantly reduced the number of CSC, but the Cisplatin effect was greater, almost eliminating this cell population in all MEC cell lines. Interestingly, the spheroid forming capacity recovered, following the combination therapy, as compared to Cisplatin alone. Our studies allowed us to conclude that the TrkB inhibition, efficiently impaired MEC cell migration, invasion and survival in vitro, however, the decrease in CSC number, following the combined treatment of ANA-12 and Cisplatin, was less than that seen with Cisplatin alone; this represents a limiting factor. (AU)

FAPESP's process: 18/15715-9 - ASSOCIATION OF BDNF/TrkB SIGNALING PATHWAY WITH TUMOR AGRESSIVENESS AND CANCER STEM CELL PROFILE OF SALIVARY GLAND CANCER
Grantee:Vivian Petersen Wagner
Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
FAPESP's process: 16/21785-4 - Association of BDNF/TRKB signaling pathway with tumor agressiveness and cancer stem cell profile of malignant salivary gland tumors
Grantee:Vivian Petersen Wagner
Support Opportunities: Scholarships in Brazil - Post-Doctoral