Ovarian cancer microenvironment: implications for cancer dissemination and chemoresistance acquisition

Abstract

Ovarian adenocarcinoma is characterized by a late detection, dissemination of cancer cells into the whole peritoneum, and the frequent acquisition of chemoresistance. If these particularities can be explained in part by intrinsic properties of ovarian cancer cells, an increased number of studies show the importance of the tumor microenvironment in tumor progression. Ovarian cancer cells can regulate the composition of their stroma in promoting the formation of ascitic fluid, rich in cytokines and bioactive lipids, and in stimulating the differentiation of stromal cells into a pro-tumoral phenotype. In return, cancer-associated fibroblasts, cancer-associated mesenchymal stem cells, tumor-associated macrophages, or other peritoneal cells, such as adipocytes and mesothelial cells can regulate tumor growth, angiogenesis, dissemination, and chemoresistance. This review focuses on the current knowledge about the roles of stromal cells and the associated secreted factors on tumor progression. We also summarize the different studies showing that targeting the microenvironment represents a great potential for improving the prognosis of patients with ovarian adenocarcinoma.

Effect of IL-6 and IL-8 on the expression of the complement activation inhibitors MAC-inhibitory protein and decay-accelerating factor in ovarian cancer A2780 cells

“…It has been widely reported that IL-6 and IL-8 reinforce the proliferation of ovarian cancer cells (11). However, the present study demonstrated that IL-6 and IL-8 did not affect ovarian cancer A2780 cell proliferation (Fig.…”

“…The key cytokines in this regulation appear to be interleukins-6 and 8 (IL-6 and IL-8), since increased levels of these cytokines have been identified in the ascites fluid of ovarian cancer patients (10,11). In vitro IL-6 is secreted by mesothelial cells, fibroblasts, macrophages and ovarian tumour cells, while IL-8 is secreted by endothelial cells and mesothelial cells, monocytes and ovarian tumour cells (11). Therefore, the tumour microenvironment is significant in all processes of ovarian cancer progression.…”

Endothelin A Receptor/β-Arrestin Signaling to the Wnt Pathway Renders Ovarian Cancer Cells Resistant to Chemotherapy

“…Selective ET A R blockade could tilt the balance toward ET B R signaling in the tumor microenvironment, including the recruitment of antitumor T cells (10,11). Besides the intrinsic mechanisms activated in EOC cells, acquisition of chemoresistance could be dependent also by the tumor microenvironment (44). In this regard, recent studies demonstrated that endothelial cells chemoprotect tumor cells through activation of ET-1 axis (45).…”

Cancer-associated fibroblasts regulate endothelial adhesion protein LPP to promote ovarian cancer chemoresistance

“…The ovarian tumor microenvironment, which is composed primarily of fibroblasts, ECM proteins, endothelial cells, and lymphocytic infiltrates, can regulate tumor growth, angiogenesis, dissemination, and chemoresistance (11,16). CAFs have been shown to play crucial roles in cancer progression.…”