Ovarian Cancer Dissemination—A Cell Biologist’s Perspective

Abstract

Epithelial ovarian cancer (EOC) comprises multiple disease states representing a variety of distinct tumors that, irrespective of tissue of origin, genetic aberrations and pathological features, share common patterns of dissemination to the peritoneal cavity. EOC peritoneal dissemination is a stepwise process that includes the formation of malignant outgrowths that detach and establish widespread peritoneal metastases through adhesion to serosal membranes. The cell biology associated with outgrowth formation, detachment, and de novo adhesion is at the nexus of diverse genetic backgrounds that characterize the disease. Development of treatment for metastatic disease will require detailed characterization of cellular processes involved in each step of EOC peritoneal dissemination. This article offers a review of the literature that relates to the current stage of knowledge about distinct steps of EOC peritoneal dissemination, with emphasis on the cell biology aspects of the process.

The CCL5/CCR5 Axis in Cancer Progression

“…Peritoneal dissemination is the most common mechanism of disease progression in ovarian cancer [178]. It is associated with the development of malignant ascites, which is a major cause of chemoresistance and recurrence.…”

Ovarian Cancer Cells in Ascites Form Aggregates That Display a Hybrid Epithelial-Mesenchymal Phenotype and Allows Survival and Proliferation of Metastasizing Cells

“…On the other hand, FN1 might also constitute an extracellular substrate for ovarian cancer cell aggregation in spheroids in the absence of stromal fibroblasts. It had been previously demonstrated that soluble ECM proteins, such as FN1 and vitronectin are detectable in ascitic fluid [ 28 ] and are organized by integrins for survival and proliferation (for a review see [ 44 ]). The role of endogenous FN1 in metastasis has been previously demonstrated in experimental models of ovarian cancers.…”

Ovulatory Follicular Fluid Facilitates the Full Transformation Process for the Development of High-Grade Serous Carcinoma

“…The nature of these activities is unknown. Promising candidates of non-AKT signals include soluble ECM proteins, such as laminin, fibronectin in FF [ 56 ] in promoting the adhesion, spreading, and migration of tumor cells via FAK [ 16 , 57 , 58 , 59 ].…”

“…Indeed, exfoliated STIC cells are frequently found in the lumen of the fallopian tube [ 15 ]. This demonstrates the following model of STIC metastasis: a long-term, constant shedding of STIC cells into the peritoneal cavity, which leads to anoikis until tumor cells have evolved to survive, ability of attachment and growth in the new microenvironment on the peritoneal or ovarian surface, and invasion into the underlying stroma to establish metastasis [ 16 ]. This characteristic shedding-and-seeding mechanism of STIC metastasis differs much from the classical invasion-and-intravasation mechanism of other in situ carcinomas, and this will be a focus of our study.…”