Ovarian Cancer-Associated Mesothelial Cells: Transdifferentiation to Minions of Cancer and Orchestrate Developing Peritoneal Dissemination

Abstract

Ovarian cancer has one of the poorest prognoses among carcinomas. Advanced ovarian cancer often develops ascites and peritoneal dissemination, which is one of the poor prognostic factors. From the perspective of the “seed and soil” hypothesis, the intra-abdominal environment is like the soil for the growth of ovarian cancer (OvCa) and mesothelial cells (MCs) line the top layer of this soil. In recent years, various functions of MCs have been reported, including supporting cancer in the OvCa microenvironment. We refer to OvCa-associated MCs (OCAMs) as MCs that are stimulated by OvCa and contribute to its progression. OCAMs promote OvCa cell adhesion to the peritoneum, invasion, and metastasis. Elucidation of these functions may lead to the identification of novel therapeutic targets that can delay OvCa progression, which is difficult to cure.

Tumor-Associated Macrophages (TAMs) in Colorectal Cancer (CRC): From Mechanism to Therapy and Prognosis

“…The components of the tumor microenvironment include all of the nonmalignant stroma cells inside the tumor other than the tumor cells, including fibroblasts, endothelial cells, immune cells, and platelets [5,6]. Paget proposed the "seed and soil" theory in 1889 and conducted an indepth analysis of the molecular characteristics of "seeds" (cancer cells) [7][8][9][10][11]. By studying the "soil" formed by cancer cells and host immune cells, scientists found that immune cells usually bind to cancer cells and obtain specific biological phenotypes via interactions with them.…”

Ovarian Cancer-Driven Mesothelial-to-Mesenchymal Transition is Triggered by the Endothelin-1/β-arr1 Axis

“…SOC cells exfoliate as single cells or multicellular spheroids that disseminate with the peritoneal fluid flow ( Ahmed and Stenvers, 2013 ; Worzfeld et al, 2017 ; Rickard et al, 2021 ). Metastatic spread is largely mediated by the ability of spheroids, but also individual cells, to adhere to a monolayer of peritoneal mesothelial cells (MCs) resting upon a basement membrane, to induce their retraction and to penetrate the sub-mesothelial interstitial collagen-rich extracellular matrix (ECM), followed by their survival, and tumor nodule formation with surrounding host cells ( Burleson et al, 2004 ; Shield et al, 2009 ; Mogi et al, 2021 ). In this context, the invasive behaviour of SOC spheroids depends upon their contractile capacity and involves both integrins and cadherins ( Sodek et al, 2009 ; Iwanicki et al, 2011 ; Klymenko et al, 2017a ; Klymenko et al, 2017b ; SacksSuarez et al, 2019 ; Goyeneche et al, 2020 ).…”

“…Although for many years mesothelial tissue has been considered as a sheet of cells with low mobility, serving as a barrier against tumors, recent studies demonstrated that they can be reprogrammed by TME to acquire invasive properties and tumor-supporting functions, mainly in the advanced stages of SOC tumor, which is likely to develop peritoneal dissemination ( Rynne-Vidal et al, 2015 ; Mogi et al, 2021 ). MCs might be altered by SOC cells through the stimulation of soluble factors present in ascites ( Matte et al, 2014 ; Matte et al, 2019 ).…”

A large-scale multi-institutional study evaluating prognostic aspects of positive ascites cytology and effects of therapeutic interventions in epithelial ovarian cancer

“…OvCa cells released and floating in ascites have metastatic potential to the peritoneum 11 . The amount of tumor cells in the peritoneum, which is dependent on the total tumor mass in the peritoneum, is associated with the positivity rate on cytology.…”