Development of Peritoneal Carcinomatosis in Epithelial Ovarian Cancer: A Review

Abstract

Epithelial ovarian cancer (EOC) metastasizes intra-abdominally with often numerous, superficial, small-sized lesions. This so-called peritoneal carcinomatosis is difficult to treat, and peritoneal recurrences are frequently observed, leading to a poor prognosis. Underlying mechanisms of interactions between EOC and peritoneal cells are incompletely understood. This review summarizes and discusses the development of peritoneal carcinomatosis from a cell-biological perspective, focusing on characteristics of EOC and peritoneal cells. We aim to provide insight into how peritoneum facilitates tumor adhesion but limits size of lesions and depth of invasion. The development of peritoneal carcinomatosis is a multistep process that requires adaptations of EOC and peritoneal cells. Mechanisms that enable tumor adhesion and growth involve cadherin restructuring on EOC cells, integrin-mediated adhesion, and mesothelial evasion by mechanical forces driven by integrin-ligand interactions. Clinical trials targeting these mechanisms, however, showed only limited effects. Other factors that inhibit tumor growth and deep invasion are virtually unknown. Future studies are needed to elucidate the exact mechanisms that underlie the development and limited growth of peritoneal carcinomatosis. This review on development of peritoneal carcinomatosis of EOC summarizes the current knowledge and its limitations. Clarification of the stepwise process may inspire future research to investigate new treatment approaches of peritoneal carcinomatosis.

The lipid kinase PI3Kα is required for the cohesion and survival of cancer cells disseminated in serous cavities

“…P-cadherin expression promotes migratory potential and aggregation of circulating ovarian cancer cells into multicellular aggregates (57). These elements highlighting actin role could in part explain PI3Kα involvement in cell clustering (58,59).…”

Connecting the Microenvironmental Niche to Treatment Response in Ovarian Cancer

“…Many stromal agents play a role in the development of ovarian cancer such as vasculature, collagen, fibroblasts, cytokines, and T-cell infiltration [2], [9], [10]. The role of all of these factors are challenging to experimentally dissect, as they form a complex, interlinked system (see [9], [11] for a review).…”

“…However, early detection before metastases occur is challenging for a variety of reasons; nevertheless, only 15% of cases are discovered in an early stage [1]. The majority of patients (85%) present with Stage 3 or 4 cancer and excessive metastases into the peritoneum, the lining of the cavity between the visceral organs and the abdominal wall [2], [3]. Intraperitoneal metastases are difficult to treat, and recurrence is frequent, with only ~29% survival at 5 years [1].…”

“…All ovarian cancers share a common growth pattern, in which the cancer first develops in the fallopian tube or on the ovaries. Subsequently it metastasizes into the peritoneal cavity either through the basement membrane or by exfoliation into the peritoneal fluid [2], [4]. Occasionally metastatic sites also form in more distant locations, such as the brain, liver, or lung [2], however this occurs in only ~15% of patients [5].…”

“…Subsequently it metastasizes into the peritoneal cavity either through the basement membrane or by exfoliation into the peritoneal fluid [2], [4]. Occasionally metastatic sites also form in more distant locations, such as the brain, liver, or lung [2], however this occurs in only ~15% of patients [5]. The cells forming the seeds for more distant metastases are derived either from the primary tumor, or from a secondary site in the peritoneum [6].…”