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Identification of novel candidate targets for suppressing ovarian cancer progression through IL-33/ST2 axis components using the system biology approach
Background: Cancer-associated fibroblasts (CAFs) of ovarian cancer (OvC) are the most prevalent element of the tumor microenvironment (TM). By promoting angiogenesis, immunological suppression, and invasion, CAFs speed up the growth of tumors by changing the extracellular matrix’s structure and comp...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10272621/ https://www.ncbi.nlm.nih.gov/pubmed/37333018 http://dx.doi.org/10.3389/fmolb.2023.1189527 |
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author | Reivan Ortiz, Geovanny Genaro Ciongradi, Carmen Iulia Chaitanya, M. V. N. L. Narayanan, Jayasankar Mohany, Mohamed Al-Rejaie, Salim S. Arias-Gonzáles, José Luis Sârbu, Ioan Assefi, Marjan Akram, Shaik Vaseem Döğüş, Yusuf Bahrami, Abolfazl Akhavan-Sigari, Reza |
author_facet | Reivan Ortiz, Geovanny Genaro Ciongradi, Carmen Iulia Chaitanya, M. V. N. L. Narayanan, Jayasankar Mohany, Mohamed Al-Rejaie, Salim S. Arias-Gonzáles, José Luis Sârbu, Ioan Assefi, Marjan Akram, Shaik Vaseem Döğüş, Yusuf Bahrami, Abolfazl Akhavan-Sigari, Reza |
author_sort | Reivan Ortiz, Geovanny Genaro |
collection | PubMed |
description | Background: Cancer-associated fibroblasts (CAFs) of ovarian cancer (OvC) are the most prevalent element of the tumor microenvironment (TM). By promoting angiogenesis, immunological suppression, and invasion, CAFs speed up the growth of tumors by changing the extracellular matrix’s structure and composition and/or initiating the epithelial cells (EPT). IL-33/ST2 signaling has drawn a lot of attention since it acts as a pro-tumor alarmin and encourages spread by altering TM. Methods: Differentially expressed genes (DEGs) of the OvC tumor microenvironment were found in the GEO database, qRT-PCR, western blotting, and immunohistochemistry, and their presence and changes in healthy and tumor tissue content were examined. Primary cultures of healthy fibroblasts and CAFs obtained from healthy and tumor tissues retrieved from OvC samples were used for in vitro and in vivo investigations. Cultured primary human CAFs were utilized to investigate the regulation and the IL-33/ST2 axis role in the inflammation reactions. Results: Although ST2 and IL-33 expression was detected in both epithelial (EPT) and fibroblast cells of ovarian cancer, they are more abundant in CAFs. Lipopolysaccharides, serum amyloid A1, and IL-1β, the inflammatory mediators, could all induce IL-33 expression through NF-κB activation in human CAFs. In turn, via the ST2 receptor, IL-33 affected the production of IL-6, IL-1β, and PTGS2 in human CAFs via the MAPKs-NF-κB pathway. Conclusion: Our findings suggest that IL-33/ST2 is affected by the interaction of CAFs and epithelial cells inside the tumor microenvironment. Activation of this axis leads to increased expression of inflammatory factors in tumor CAFs and EPT cells. Therefore, targeting the IL-33/ST2 axis could have potential value in the prevention of OvC progression. |
format | Online Article Text |
id | pubmed-10272621 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-102726212023-06-17 Identification of novel candidate targets for suppressing ovarian cancer progression through IL-33/ST2 axis components using the system biology approach Reivan Ortiz, Geovanny Genaro Ciongradi, Carmen Iulia Chaitanya, M. V. N. L. Narayanan, Jayasankar Mohany, Mohamed Al-Rejaie, Salim S. Arias-Gonzáles, José Luis Sârbu, Ioan Assefi, Marjan Akram, Shaik Vaseem Döğüş, Yusuf Bahrami, Abolfazl Akhavan-Sigari, Reza Front Mol Biosci Molecular Biosciences Background: Cancer-associated fibroblasts (CAFs) of ovarian cancer (OvC) are the most prevalent element of the tumor microenvironment (TM). By promoting angiogenesis, immunological suppression, and invasion, CAFs speed up the growth of tumors by changing the extracellular matrix’s structure and composition and/or initiating the epithelial cells (EPT). IL-33/ST2 signaling has drawn a lot of attention since it acts as a pro-tumor alarmin and encourages spread by altering TM. Methods: Differentially expressed genes (DEGs) of the OvC tumor microenvironment were found in the GEO database, qRT-PCR, western blotting, and immunohistochemistry, and their presence and changes in healthy and tumor tissue content were examined. Primary cultures of healthy fibroblasts and CAFs obtained from healthy and tumor tissues retrieved from OvC samples were used for in vitro and in vivo investigations. Cultured primary human CAFs were utilized to investigate the regulation and the IL-33/ST2 axis role in the inflammation reactions. Results: Although ST2 and IL-33 expression was detected in both epithelial (EPT) and fibroblast cells of ovarian cancer, they are more abundant in CAFs. Lipopolysaccharides, serum amyloid A1, and IL-1β, the inflammatory mediators, could all induce IL-33 expression through NF-κB activation in human CAFs. In turn, via the ST2 receptor, IL-33 affected the production of IL-6, IL-1β, and PTGS2 in human CAFs via the MAPKs-NF-κB pathway. Conclusion: Our findings suggest that IL-33/ST2 is affected by the interaction of CAFs and epithelial cells inside the tumor microenvironment. Activation of this axis leads to increased expression of inflammatory factors in tumor CAFs and EPT cells. Therefore, targeting the IL-33/ST2 axis could have potential value in the prevention of OvC progression. Frontiers Media S.A. 2023-06-02 /pmc/articles/PMC10272621/ /pubmed/37333018 http://dx.doi.org/10.3389/fmolb.2023.1189527 Text en Copyright © 2023 Reivan Ortiz, Ciongradi, Chaitanya, Narayanan, Mohany, Al-Rejaie, Arias-Gonzáles, Sârbu, Assefi, Akram, Döğüş, Bahrami and Akhavan-Sigari. 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 | Molecular Biosciences Reivan Ortiz, Geovanny Genaro Ciongradi, Carmen Iulia Chaitanya, M. V. N. L. Narayanan, Jayasankar Mohany, Mohamed Al-Rejaie, Salim S. Arias-Gonzáles, José Luis Sârbu, Ioan Assefi, Marjan Akram, Shaik Vaseem Döğüş, Yusuf Bahrami, Abolfazl Akhavan-Sigari, Reza Identification of novel candidate targets for suppressing ovarian cancer progression through IL-33/ST2 axis components using the system biology approach |
title | Identification of novel candidate targets for suppressing ovarian cancer progression through IL-33/ST2 axis components using the system biology approach |
title_full | Identification of novel candidate targets for suppressing ovarian cancer progression through IL-33/ST2 axis components using the system biology approach |
title_fullStr | Identification of novel candidate targets for suppressing ovarian cancer progression through IL-33/ST2 axis components using the system biology approach |
title_full_unstemmed | Identification of novel candidate targets for suppressing ovarian cancer progression through IL-33/ST2 axis components using the system biology approach |
title_short | Identification of novel candidate targets for suppressing ovarian cancer progression through IL-33/ST2 axis components using the system biology approach |
title_sort | identification of novel candidate targets for suppressing ovarian cancer progression through il-33/st2 axis components using the system biology approach |
topic | Molecular Biosciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10272621/ https://www.ncbi.nlm.nih.gov/pubmed/37333018 http://dx.doi.org/10.3389/fmolb.2023.1189527 |
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