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Detection of Carcinoma-Associated Fibroblasts Derived from Mesothelial Cells via Mesothelial-to-Mesenchymal Transition in Primary Ovarian Carcinomas
by
, , and
Henar Tomero-Sanz
1
,
José Antonio Jiménez-Heffernan
2,
María Concepción Fernández-Chacón
3,
Ignacio Cristóbal-García
3,
Ricardo Sainz de la Cuesta
4,5,
Lucía González-Cortijo
4,5,
Manuel López-Cabrera
1,* and
Pilar Sandoval
1,* 1
Tissue and Organ Homeostasis Program, Centro de Biología Molecular Severo Ochoa (CBM), CSIC-UAM, 28049 Madrid, Spain
2
Department of Pathology, Hospital Universitario La Princesa, 28006 Madrid, Spain
3
Hospital Universitario de la Zarzuela, 28023 Madrid, Spain
4
Hospital Universitario QuirónSalud Madrid, 28223 Madrid, Spain
5
Department of de Medicine, Facultad de Biomédica y Ciencias de la Salud, Universidad Europea de Madrid, 28670 Madrid, Spain
*
Authors to whom correspondence should be addressed.
Cancers 2024, 16(15), 2697; https://doi.org/10.3390/cancers16152697
Submission received: 29 May 2024
/
Revised: 23 July 2024
/
Accepted: 27 July 2024
/
Published: 29 July 2024
(This article belongs to the Special Issue Multiple Signaling Pathways in Ovarian Cancer)
Simple Summary
Approximately 70–80% of patients with epithelial ovarian cancer (OC) experience peritoneal metastasis. Identification of mesothelial-to-mesenchymal transition (MMT) in the peritoneum may guide the accurate treatment and follow-up of patients with advanced OC. The aim of this study was to evaluate whether MMT took place in primary OC biopsies. We suggest the identified mesothelial-derived carcinoma-associated fibroblasts in primary tumors could impact the clinical progression of patients with OC.
Abstract
Carcinoma-associated fibroblasts (CAFs) are highly accumulated in the tumor-surrounding stroma of primary epithelial ovarian cancer (OC). CAFs exert important functions for the vascularization, growth, and progression of OC cells. However, the origin of CAFs in primary OC had not yet been studied, and they were assumed to arise from the activation of resident fibroblasts. Here, we compared CAFs in the ovary to CAFs found in peritoneal metastases from patients with advanced OC. Our findings show that CAFs from primary tumors and peritoneal metastases share the expression of mesothelial markers. Therefore, similar to peritoneal carcinomatosis, CAFs in primary ovarian carcinomas may originate from mesothelial cells via a mesothelial-to-mesenchymal transition. The detection of mesothelial-derived CAFs in tumors confined to the ovary and identification of biomarkers could be the key to the early detection of OC and peritoneal spread.
