Molecular Mechanisms Regulating Organ-Specific Metastases in Epithelial Ovarian Carcinoma

Abstract

Epithelial ovarian carcinoma is the most predominant type of ovarian carcinoma, the deadliest gynecologic malignancy. It is typically diagnosed late when the cancer has already metastasized. Transcoelomic metastasis is the most predominant mechanism of dissemination from epithelial ovarian carcinoma, although both hematogenously and lymphogenously spread metastases also occur. In this review, we describe molecular mechanisms known to regulate organ-specific metastasis from epithelial ovarian carcinoma. We begin by discussing the sites colonized by metastatic ovarian carcinoma and rank them in the order of prevalence. Next, we review the mechanisms regulating the transcoelomic metastasis. Within this chapter, we specifically focus on the mechanisms that were demonstrated to regulate peritoneal adhesion—one of the first steps in the transcoelomic metastatic cascade. Furthermore, we describe mechanisms of the transcoelomic metastasis known to regulate colonization of specific sites within the peritoneal cavity, including the omentum. Mechanisms underlying hematogenous and lymphogenous metastatic spread are less comprehensively studied in ovarian cancer, and we summarize mechanisms that were identified to date. Lastly, we discuss the outcomes of the clinical trials that attempted to target some of the mechanisms described in this review.

Ovarian Cancer, Cancer Stem Cells and Current Treatment Strategies: A Potential Role of Magmas in the Current Treatment Methods

“…Metastases in HGSOC occur through several distinct routes, which include, transcoelomic, hematogenous and lymphogenous spread [89]. The spread of OC occurs primarily through transcoelomic route, which involves metastasis in the peritoneal cavity and the surrounding peritoneal organs [90,91].…”

Development and Validation of Nomograms to Predict Lung Metastases in Patients with Ovarian Cancer: A Large Cohort Study

“…Previous studies have shown that poor differentiation and lymph node involvement are risk factors for distant metastasis 3 .We found that liver metastases, brain metastases and bone metastases are risk factors for lung metastases. If distant metastasis occurs in other parts, it means that cancer cells have spread 18 ,and the possibility of lung metastases will be higher.…”

Low centrosome numbers correlate with higher aggressivity in ovarian cancer

“…Ovarian tumors do not show typical invasion features seen in other tumor types 63 . Indeed peritoneal metastases via transcoelomic dissemination appear to be a characteristic of HGSOCs 55,64 , where tumor cells detach from the primary tumor, using the ascitic fluid as a carrier to reach mesothelial cells that line the peritoneal cavity 56,65 .…”

“…EOCs undergo a particular mode of motility, where tumor cell invade the peritoneal cavity through a process called tumor dissemination 55 . Indeed tumor cells detach from the primary tumor site, adhere and go through mesothelial cells that enclose peritoneal organs 56 .…”