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.

Keywords: gene expression; liver; lung; lymph node; mesothelium; omentum; organ-specific metastases; ovarian cancer; peritoneal adhesion; peritoneal wall.

Figure 1

A scheme of the peritoneal metastasis through the transcoelomic route. Disseminating epithelial ovarian carcinoma (EOC) cells and spheroids are shown in mauve, mesothelial cells are shown in green, the basement membrane is shown in orange, stromal cells are shown in grey, parenchymal cells are shown in yellow, and the extracellular matrix is shown in grey.

Figure 2

Molecular mechanisms regulating peritoneal adhesion. Disseminating epithelial ovarian cancer cells and spheroids are shown in mauve, mesothelial cells are shown in green, the basement membrane is shown in orange, stromal cells are shown in grey, parenchymal cells are shown in yellow, and the extracellular matrix is shown in grey. Only one interaction between a cancer cell and a mesothelial cell is shown for simplicity and a clearer presentation of the known mechanisms. CD44: CD44 molecule; CA125: mucin 16, cell surface associated or ovarian carcinoma antigen CA125; L1CAM: L1 cell adhesion molecule; CX₃CL1: C-X3-C motif chemokine ligand 1; CX₃CR1: C-X3-C motif chemokine receptor 1; CD24: CD24 molecule.