The Transcoelomic Ecosystem and Epithelial Ovarian Cancer Dissemination

Abstract

Epithelial ovarian cancer (EOC) is considered the deadliest gynecological disease and is normally diagnosed at late stages, at which point metastasis has already occurred. Throughout disease progression, EOC will encounter various ecosystems and the communication between cancer cells and these microenvironments will promote the survival and dissemination of EOC. The primary tumor is thought to develop within the ovaries or the fallopian tubes, both of which provide a microenvironment with high risk of causing DNA damage and enhanced proliferation. EOC disseminates by direct extension from the primary tumors, as single cells or multicellular aggregates. Under the influence of cellular and non-cellular factors, EOC spheroids use the natural flow of peritoneal fluid to reach distant organs within the peritoneal cavity. These cells can then implant and seed distant organs or tissues, which develop rapidly into secondary tumor nodules. The peritoneal tissue and the omentum are two common sites of EOC metastasis, providing a microenvironment that supports EOC invasion and survival. Current treatment for EOC involves debulking surgery followed by platinum-taxane combination chemotherapy; however, most patients will relapse with a chemoresistant disease with tumors developed within the peritoneum. Therefore, understanding the role of the unique microenvironments that promote EOC transcoelomic dissemination is important in improving patient outcomes from this disease. In this review article, we address the process of ovarian cancer cellular fate at the site of its origin in the secretory cells of the fallopian tube or in the ovarian surface epithelial cells, their detachment process, how the cells survive in the peritoneal fluid avoiding cell death triggers, and how cancer- associated cells help them in the process. Finally, we report the mechanisms used by the ovarian cancer cells to adhere and migrate through the mesothelial monolayer lining the peritoneum. We also discuss the involvement of the transcoelomic ecosystem on the development of chemoresistance of EOC.

Ovarian cancer relies on the PDGFRβ–fibronectin axis for tumorsphere formation and metastatic spread

“…complications [2,3,37,38]. However, the molecular mechanisms that direct tumorsphere formation and proliferation in the ascitic liquid are poorly known, and a better understanding of them will provide us with tools to block ovarian cancer progression and metastasis [2,28,29,30,31,32].…”

MNRR1 is a driver of ovarian cancer progression

“…Ovarian cancer is a solid tumor with a unique mode of metastasis formation. Unlike breast and prostate cancers, for instance, which preferentially metastasize via the hematogenous route, ovarian cancer cells typically exhibit trans-coelomic metastasis and mostly remain in the peritoneal cavity [ 8 , 9 ]. Although the process of epithelial-mesenchymal transition (EMT) has been implicated in ovarian cancer metastasis, with the loss of E-cadherin and subsequent mesenchymal reprogramming being known to enhance detachment from the primary site and support establishment on secondary sites [ 10 , 11 ], there are no clinically targetable drivers to date proven to limit ovarian cancer metastasis formation.…”

Improving SERS biosensors for the analysis of ovarian cancer-derived small extracellular vesicles

“…Ovarian cancer (OVC), a type of gynecological disease, was the cause of 200 000 deaths in women in 2020, 1 being predicted to exceed 300 000 deaths by 2035. 2,3 OVC is a silent killer because it does not develop any obvious symptoms at an early stage, resulting in a late diagnosis for most patients.…”