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Human cytomegalovirus infection enhances 5-lipoxygenase and cycloxygenase-2 expression in colorectal cancer

Colorectal cancer (CRC) is one of the most common and fatal types of cancer. Inflammation promotes CRC development, however, the underlying etiological factors are unknown. Human cytomegalovirus (HCMV), a virus that induces inflammation and other cancer hallmarks, has been detected in several types...

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Autores principales: Pantalone, Mattia Russel, Almazan, Nerea Martin, Lattanzio, Rossano, Taher, Chato, De Fabritiis, Simone, Valentinuzzi, Silvia, Bishehsari, Faraz, Mahdavinia, Mahboobeh, Verginelli, Fabio, Rahbar, Afsar, Mariani-Costantini, Renato, Söderberg-Naucler, Cecilia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10546380/
https://www.ncbi.nlm.nih.gov/pubmed/37654195
http://dx.doi.org/10.3892/ijo.2023.5564
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author Pantalone, Mattia Russel
Almazan, Nerea Martin
Lattanzio, Rossano
Taher, Chato
De Fabritiis, Simone
Valentinuzzi, Silvia
Bishehsari, Faraz
Mahdavinia, Mahboobeh
Verginelli, Fabio
Rahbar, Afsar
Mariani-Costantini, Renato
Söderberg-Naucler, Cecilia
author_facet Pantalone, Mattia Russel
Almazan, Nerea Martin
Lattanzio, Rossano
Taher, Chato
De Fabritiis, Simone
Valentinuzzi, Silvia
Bishehsari, Faraz
Mahdavinia, Mahboobeh
Verginelli, Fabio
Rahbar, Afsar
Mariani-Costantini, Renato
Söderberg-Naucler, Cecilia
author_sort Pantalone, Mattia Russel
collection PubMed
description Colorectal cancer (CRC) is one of the most common and fatal types of cancer. Inflammation promotes CRC development, however, the underlying etiological factors are unknown. Human cytomegalovirus (HCMV), a virus that induces inflammation and other cancer hallmarks, has been detected in several types of malignancy, including CRC. The present study investigated whether HCMV infection was associated with expression of the pro-inflammatory enzymes 5-lipoxygenase (5-LO) and cyclooxygenase-2 (COX-2) and other molecular, genetic and clinicopathological CRC features. The present study assessed 146 individual paraffin-embedded CRC tissue microarray (TMA) cores already characterized for TP53 and KRAS mutations, microsatellite instability (MSI) status, Ki-67 index and EGFR by immunohistochemistry (IHC). The cores were further analyzed by IHC for the expression of two HCMV proteins (Immediate Early, IE and pp65) and the inflammatory markers 5-LO and COX-2. The CRC cell lines Caco-2 and LS-174T were infected with HCMV strain VR1814, treated with antiviral drug ganciclovir (GCV) and/or anti-inflammatory drug celecoxib (CCX) and analyzed by reverse transcription-quantitative PCR and immunofluorescence for 5-LO, COX-2, IE and pp65 transcripts and proteins. HCMV IE and pp65 proteins were detected in ~90% of the CRC cases tested; this was correlated with COX-2, 5-LO and KI-67 expression, but not with EGFR immunostaining, TP53 and KRAS mutations or MSI status. In vitro, HCMV infection upregulated 5-LO and COX-2 transcript and proteins in both Caco-2 and LS-174T cells and enhanced cell proliferation as determined by MTT assay. Treatment with GCV and CCX significantly decreased the transcript levels of COX-2, 5-LO, HCMV IE and pp65 in infected cells. HCMV was widely expressed in CRC and may promote inflammation and serve as a potential new target for CRC therapy.
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spelling pubmed-105463802023-10-04 Human cytomegalovirus infection enhances 5-lipoxygenase and cycloxygenase-2 expression in colorectal cancer Pantalone, Mattia Russel Almazan, Nerea Martin Lattanzio, Rossano Taher, Chato De Fabritiis, Simone Valentinuzzi, Silvia Bishehsari, Faraz Mahdavinia, Mahboobeh Verginelli, Fabio Rahbar, Afsar Mariani-Costantini, Renato Söderberg-Naucler, Cecilia Int J Oncol Articles Colorectal cancer (CRC) is one of the most common and fatal types of cancer. Inflammation promotes CRC development, however, the underlying etiological factors are unknown. Human cytomegalovirus (HCMV), a virus that induces inflammation and other cancer hallmarks, has been detected in several types of malignancy, including CRC. The present study investigated whether HCMV infection was associated with expression of the pro-inflammatory enzymes 5-lipoxygenase (5-LO) and cyclooxygenase-2 (COX-2) and other molecular, genetic and clinicopathological CRC features. The present study assessed 146 individual paraffin-embedded CRC tissue microarray (TMA) cores already characterized for TP53 and KRAS mutations, microsatellite instability (MSI) status, Ki-67 index and EGFR by immunohistochemistry (IHC). The cores were further analyzed by IHC for the expression of two HCMV proteins (Immediate Early, IE and pp65) and the inflammatory markers 5-LO and COX-2. The CRC cell lines Caco-2 and LS-174T were infected with HCMV strain VR1814, treated with antiviral drug ganciclovir (GCV) and/or anti-inflammatory drug celecoxib (CCX) and analyzed by reverse transcription-quantitative PCR and immunofluorescence for 5-LO, COX-2, IE and pp65 transcripts and proteins. HCMV IE and pp65 proteins were detected in ~90% of the CRC cases tested; this was correlated with COX-2, 5-LO and KI-67 expression, but not with EGFR immunostaining, TP53 and KRAS mutations or MSI status. In vitro, HCMV infection upregulated 5-LO and COX-2 transcript and proteins in both Caco-2 and LS-174T cells and enhanced cell proliferation as determined by MTT assay. Treatment with GCV and CCX significantly decreased the transcript levels of COX-2, 5-LO, HCMV IE and pp65 in infected cells. HCMV was widely expressed in CRC and may promote inflammation and serve as a potential new target for CRC therapy. D.A. Spandidos 2023-08-25 /pmc/articles/PMC10546380/ /pubmed/37654195 http://dx.doi.org/10.3892/ijo.2023.5564 Text en Copyright: © Pantalone et al. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.
spellingShingle Articles
Pantalone, Mattia Russel
Almazan, Nerea Martin
Lattanzio, Rossano
Taher, Chato
De Fabritiis, Simone
Valentinuzzi, Silvia
Bishehsari, Faraz
Mahdavinia, Mahboobeh
Verginelli, Fabio
Rahbar, Afsar
Mariani-Costantini, Renato
Söderberg-Naucler, Cecilia
Human cytomegalovirus infection enhances 5-lipoxygenase and cycloxygenase-2 expression in colorectal cancer
title Human cytomegalovirus infection enhances 5-lipoxygenase and cycloxygenase-2 expression in colorectal cancer
title_full Human cytomegalovirus infection enhances 5-lipoxygenase and cycloxygenase-2 expression in colorectal cancer
title_fullStr Human cytomegalovirus infection enhances 5-lipoxygenase and cycloxygenase-2 expression in colorectal cancer
title_full_unstemmed Human cytomegalovirus infection enhances 5-lipoxygenase and cycloxygenase-2 expression in colorectal cancer
title_short Human cytomegalovirus infection enhances 5-lipoxygenase and cycloxygenase-2 expression in colorectal cancer
title_sort human cytomegalovirus infection enhances 5-lipoxygenase and cycloxygenase-2 expression in colorectal cancer
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10546380/
https://www.ncbi.nlm.nih.gov/pubmed/37654195
http://dx.doi.org/10.3892/ijo.2023.5564
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