Identification of novel candidate targets for suppressing ovarian cancer progression through IL-33/ST2 axis components using the system biology approach

Frontiers in Molecular Biosciences

Molecular Biosciences

Abolfazl Bahrami¹  Yusuf Döğüş²  Reza Akhavan-Sigari³  Mohamed Mohany⁴  Salim S. Al-Rejaie⁴  Jayasankar Narayanan⁵  José Luis Arias-Gonzáles⁶  Carmen Iulia Ciongradi⁷  Ioan Sârbu⁷  Geovanny Genaro Reivan Ortiz⁸  M. V. N. L. Chaitanya⁹  Marjan Assefi^1,10  Shaik Vaseem Akram^1,11 

[1] Biomedical Center for Systems Biology Science Munich, Ludwig-Maximilians-University, Munich, Germany;Department of Medical Biochemistry, Faculty of Medicine, Cukurova University, Adana, Türkiye;Department of Neurosurgery, University Medical Center Tuebingen, Tuebingen, Germany;Department of Healthcare Management and Clinical Research, Collegium Humanum Warsaw Management University, Warsaw, Poland;Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia;Department of Pharmacology, SRM Institute of Science and Technology, SRM College of Pharmacy, Kattankulathu, Tamil Nadu, India;Department of Social Sciences, Faculty of Social Studies, University of British Columbia, Vancouver, BC, Canada;Department of Surgery-Pediatric Surgery and Orthopedics, “Grigore T. Popa” University of Medicine and Pharmacy, Iași, Romania;Laboratory of Basic Psychology, Behavioral Analysis and Programmatic Development (PAD-LAB), Catholic University of Cuenca, Cuenca, Ecuador;School of Pharmaceutical Sciences, Lovely Professional University, Phagwara, Punjab, India;University of North Carolina, Greensboro, NC, United States;Uttaranchal University, Dehradun, India;

关键词: IL-33;    ST2;    ovarian cancer;    cancer-associated fibroblasts;    MAPKs-NF-κB;    gene expression;    protein expression;   

DOI  :  10.3389/fmolb.2023.1189527

 received in 2023-03-19, accepted in 2023-05-18,  发布年份 2023

来源: Frontiers

【 摘 要 】

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.

【 授权许可】

Unknown   
Copyright © 2023 Reivan Ortiz, Ciongradi, Chaitanya, Narayanan, Mohany, Al-Rejaie, Arias-Gonzáles, Sârbu, Assefi, Akram, Döğüş, Bahrami and Akhavan-Sigari.