Cancer Associated Fibroblasts: Naughty Neighbors That Drive Ovarian Cancer Progression

Abstract

Ovarian cancer is the most lethal gynecologic malignancy, and patient prognosis has not improved significantly over the last several decades. In order to improve therapeutic approaches and patient outcomes, there is a critical need for focused research towards better understanding of the disease. Recent findings have revealed that the tumor microenvironment plays an essential role in promoting cancer progression and metastasis. The tumor microenvironment consists of cancer cells and several different types of normal cells recruited and reprogrammed by the cancer cells to produce factors beneficial to tumor growth and spread. These normal cells present within the tumor, along with the various extracellular matrix proteins and secreted factors, constitute the tumor stroma and can compose 10⁻60% of the tumor volume. Cancer associated fibroblasts (CAFs) are a major constituent of the tumor microenvironment, and play a critical role in promoting many aspects of tumor function. This review will describe the various hypotheses about the origin of CAFs, their major functions in the tumor microenvironment in ovarian cancer, and will discuss the potential of targeting CAFs as a possible therapeutic approach.

Keywords: ECM; angiogenesis; cancer associated fibroblasts; chemoresistance; cross-talk; fibroblast; invasion; ovarian cancer; therapy; tumor microenvironment.

Figure 1

Formation of cancer associated fibroblasts (CAFs) through the reprogramming of resident normal fibroblasts or mesenchymal stem cells by ovarian cancer cells. TGF-β: transforming growth factor beta; PDGF: platelet-derived growth factor; FGF: fibroblast growth factor; EGF: epidermal growth factors; CXCL12: C-X-C Motif Chemokine Ligand 12; CCL5: C-C Motif Chemokine Ligand 5; ↑: upregulated;↓: downregulated.

Figure 2

Functions of CAFs contributing towards tumor progression. ECM: extra cellular matrix; EMT: epithelial–mesenchymal transition.