Role of cancer-associated fibroblasts in tumor structure, composition and the microenvironment in ovarian cancer

Ovarian cancer (OVAC) remains the most lethal gynecological malignancy; it is ranked fifth among the most common types of cancer that affect women worldwide. Several aspects of the disease, including molecular pathogenesis, epidemiology, histological subtypes, poor prognosis at early stages due to the absence of specific signs and symptoms, and curative treatments in the advanced stages are all responsible for the poor survival rate, which is evaluated to be at 5 years once the cancer is diagnosed and treatment begins. A better understanding of the pathogenesis of ovarian cancer is therefore crucial, even though unexplored pathways, in order to improve the prognosis of patients with OVAC and to develop novel therapeutic approaches. Accordingly, the tumor microenvironment, defined as the combination of proteins produced by all tumor cells and by non-cancerous cells or the stroma, and composed of several cells, including those from the immune, inflammatory and adipose systems, as well as the mesenchymal stem, endothelial and fibroblasts cells, has recently attracted attention. Of particular interest are fibroblasts, which can be activated into cancer-associated fibroblast (CAFs) to become a potent supporter of carcinogenesis, promoting the initiation of epithelial tumor formation, tumor growth, angiogenesis and metastasis, as well as therapeutic resistance and immunosuppression. Thus, the targeting of CAFs for early diagnosis and effective therapy warrants our attention. In this review, we discuss the mechanisms through which CAFs may affect the structure, composition and microenvironment of the ovarian tumor. We also aim to highlight important aspects of OVAC pathobiology involving CAFs, in an attempt to provide insight into novel diagnostic windows and provide new therapeutic perspectives.