Malignant peritoneal effusion acting as a tumor environment in ovarian cancer progression: Impact and significance

Abstract

Until recently, ovarian cancer research has mainly focused on the tumor cells themselves ignoring for the most part the surrounding tumor environment which includes malignant peritoneal effusions. However, one of the major conceptual advances in oncology over the last few years has been the appreciation that cancer progression cannot be explained by aberrations in cancer cells themselves and is strongly influenced by the surrounding tumor environment. The mechanisms of ovarian cancer progression differ from that of other solid tumors because ovarian cancer cells primarily disseminate within the peritoneal cavity. Malignant peritoneal effusion accumulates in the peritoneal cavity during ovarian cancer progression. These exudative fluids act as a unique tumor environment providing a framework that orchestrates cellular and molecular changes contributing to aggressiveness and disease progression. The composition of ascites, which includes cellular and acellular components, constantly adapts during the course of the disease in response to various cellular cues originating from both tumor and stromal cells. The tumor environment that represents peritoneal effusions closely constitute an ecosystem, with specific cell types and signaling molecules increasing and decreasing during the course of the disease progression creating a single complex network. Although recent advances aiming to understand the ovarian tumor environment have focused one at a time on components, the net impact of the whole environment cannot be understood simply from its parts or outside is environmental context.

Keywords: Ovarian cancer; Tumor environment; Peritoneal effusions; Ascites; Dissemination; Multicellular spheroids

Core tip: The malignant peritoneal effusion that accumulates during ovarian cancer dissemination and progression constitutes a unique tumor environment. Bidirectional communications between tumor cells and their surrounding environment influence ovarian cancer dissemination, progression and patient prognosis. To solve the complexity of this tumor environment and understand how it affects cancer progression, a paradigm shift is necessary. Peritoneal effusions should be studied as integrated systems with innovative modeling approaches.