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Anti-EGFR monoclonal antibody Cetuximab displays potential anti-cancer activities in feline oral squamous cell carcinoma cell lines

Feline oral squamous cell carcinoma (FOSCC) is a malignant tumor characterized by an aggressive behavior and poor prognosis, for which no fully effective therapies are available. Studies of comparative oncology suggest that epidermal growth factor receptor (EGFR) may be a therapeutic target in FOSCC...

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Autores principales: Altamura, Gennaro, Borzacchiello, Giuseppe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9712204/
https://www.ncbi.nlm.nih.gov/pubmed/36467642
http://dx.doi.org/10.3389/fvets.2022.1040552
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author Altamura, Gennaro
Borzacchiello, Giuseppe
author_facet Altamura, Gennaro
Borzacchiello, Giuseppe
author_sort Altamura, Gennaro
collection PubMed
description Feline oral squamous cell carcinoma (FOSCC) is a malignant tumor characterized by an aggressive behavior and poor prognosis, for which no fully effective therapies are available. Studies of comparative oncology suggest that epidermal growth factor receptor (EGFR) may be a therapeutic target in FOSCC, similarly to human head and neck SCC (HNSCC), where the use of anti-EGFR monoclonal antibody Cetuximab has entered the clinical practice. The aim of this study was to assess the efficacy of Cetuximab in three validated preclinical models of FOSCC (SCCF1, SCCF2, SCCF3). Sequencing of tyrosine kinase domain of EGFR in the cell lines revealed a wild-type genotype, excluding the presence of activating mutations. Western blotting experiments demonstrated that Cetuximab inhibited activation of EGFR and its downstream kinase Akt in SCCF1, SCCF2 and SCCF3 along with HNSCC cell line CAL 27 included as control. Importantly, CCK-8 and trypan blue exclusion assays revealed that treatment with Cetuximab caused a decrease in cell proliferation and cell viability in all cell lines, with a general dose- and time-dependent trend. Cell death induced by Cetuximab was associated with cleavage of PARP, indicating occurrence of apoptosis. Taken together, our data suggest that Cetuximab exerts potential anti-cancer activities in FOSCC, paving the way for future translational studies aimed at assessing its employment in the therapy of this lethal cancer of cats.
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spelling pubmed-97122042022-12-02 Anti-EGFR monoclonal antibody Cetuximab displays potential anti-cancer activities in feline oral squamous cell carcinoma cell lines Altamura, Gennaro Borzacchiello, Giuseppe Front Vet Sci Veterinary Science Feline oral squamous cell carcinoma (FOSCC) is a malignant tumor characterized by an aggressive behavior and poor prognosis, for which no fully effective therapies are available. Studies of comparative oncology suggest that epidermal growth factor receptor (EGFR) may be a therapeutic target in FOSCC, similarly to human head and neck SCC (HNSCC), where the use of anti-EGFR monoclonal antibody Cetuximab has entered the clinical practice. The aim of this study was to assess the efficacy of Cetuximab in three validated preclinical models of FOSCC (SCCF1, SCCF2, SCCF3). Sequencing of tyrosine kinase domain of EGFR in the cell lines revealed a wild-type genotype, excluding the presence of activating mutations. Western blotting experiments demonstrated that Cetuximab inhibited activation of EGFR and its downstream kinase Akt in SCCF1, SCCF2 and SCCF3 along with HNSCC cell line CAL 27 included as control. Importantly, CCK-8 and trypan blue exclusion assays revealed that treatment with Cetuximab caused a decrease in cell proliferation and cell viability in all cell lines, with a general dose- and time-dependent trend. Cell death induced by Cetuximab was associated with cleavage of PARP, indicating occurrence of apoptosis. Taken together, our data suggest that Cetuximab exerts potential anti-cancer activities in FOSCC, paving the way for future translational studies aimed at assessing its employment in the therapy of this lethal cancer of cats. Frontiers Media S.A. 2022-11-17 /pmc/articles/PMC9712204/ /pubmed/36467642 http://dx.doi.org/10.3389/fvets.2022.1040552 Text en Copyright © 2022 Altamura and Borzacchiello. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Veterinary Science
Altamura, Gennaro
Borzacchiello, Giuseppe
Anti-EGFR monoclonal antibody Cetuximab displays potential anti-cancer activities in feline oral squamous cell carcinoma cell lines
title Anti-EGFR monoclonal antibody Cetuximab displays potential anti-cancer activities in feline oral squamous cell carcinoma cell lines
title_full Anti-EGFR monoclonal antibody Cetuximab displays potential anti-cancer activities in feline oral squamous cell carcinoma cell lines
title_fullStr Anti-EGFR monoclonal antibody Cetuximab displays potential anti-cancer activities in feline oral squamous cell carcinoma cell lines
title_full_unstemmed Anti-EGFR monoclonal antibody Cetuximab displays potential anti-cancer activities in feline oral squamous cell carcinoma cell lines
title_short Anti-EGFR monoclonal antibody Cetuximab displays potential anti-cancer activities in feline oral squamous cell carcinoma cell lines
title_sort anti-egfr monoclonal antibody cetuximab displays potential anti-cancer activities in feline oral squamous cell carcinoma cell lines
topic Veterinary Science
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9712204/
https://www.ncbi.nlm.nih.gov/pubmed/36467642
http://dx.doi.org/10.3389/fvets.2022.1040552
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