Exploring the Role of Fallopian Ciliated Cells in the Pathogenesis of High-Grade Serous Ovarian Cancer

Abstract

High-grade serous epithelial ovarian cancer (HGSOC) is the fifth leading cause of cancer death in women and the first among gynecological malignancies. Despite an initial response to standard chemotherapy, most HGSOC patients relapse. To improve treatment options, we must continue investigating tumor biology. Tumor characteristics (e.g., risk factors and epidemiology) are valuable clues to accomplish this task. The two most frequent risk factors for HGSOC are the lifetime number of ovulations, which is associated with increased oxidative stress in the pelvic area caused by ovulation fluid, and a positive family history due to genetic factors. In the attempt to identify novel genetic factors (i.e., genes) associated with HGSOC, we observed that several genes in linkage with HGSOC are expressed in the ciliated cells of the fallopian tube. This finding made us hypothesize that ciliated cells, despite not being the cell of origin for HGSOC, may take part in HGSOC tumor initiation. Specifically, malfunction of the ciliary beat impairs the laminar fluid flow above the fallopian tube epithelia, thus likely reducing the clearance of oxidative stress caused by follicular fluid. Herein, we review the up-to-date findings dealing with HGSOC predisposition with the hypothesis that fallopian ciliated cells take part in HGSOC onset. Finally, we review the up-to-date literature concerning genes that are located in genomic loci associated with epithelial ovarian cancer (EOC) predisposition that are expressed by the fallopian ciliated cells.

Comparing Paclitaxel–Carboplatin with Paclitaxel–Cisplatin as the Front-Line Chemotherapy for Patients with FIGO IIIC Serous-Type Tubo-Ovarian Cancer

“…Serous-type is the most common subtype among EOCs in general; however, endometriosis-associated EOCs, such as clear cell type or endometrioid type are relatively common in certain populations, including Taiwan and Japan [7][8][9][10][11]. Clinically, the serous-type EOC and primary peritoneal serous carcinoma (PPSC) and primary Fallopian tube cancer (PFTC) are often considered the same group disease, based on the similar clinical behavior and possibly sharing the similar pathogenesis [12][13][14][15][16][17][18]. In 1996, McGuire and colleagues conducted a clinical trial to set up the standard therapy for patients with ETOC, including primary debulking surgery (PDS), also called primary cytoreductive surgery (PCS) plus adjuvant triweekly paclitaxel and cisplatin therapy [19].…”

Loss of tubal ciliated cells as a risk for “ovarian” or pelvic serous carcinoma

“…Some other earlier studies showed that primary cilia may play a critical role in tumorigenesis and cancer progression by functioning as a tumor suppressor organelle that regulates cell cycle/proliferation, differentiation, polarity, and migration (38,39). On the other hand, loss of tubal ciliated cells may also reduce the capacity of removing follicular uid induced genotoxicity within the fallopian tube (40). In one of our studies about ovarian serous carcinogenesis, we also notice that gradual motile cilia loss from serous cystadenoma to serous borderline tumor and nally complete loss of cilia in low-grade serous carcinoma (5).…”

<p>LncRNA GAS8-AS1 Inhibits Ovarian Cancer Progression Through Activating Beclin1-Mediated Autophagy</p>

“…Ovarian cancer is the leading cause of death in female genital tumors. 28 The first chemotherapy is effective for most patients, but about 70% of patients will relapse within a few months after the first chemotherapy, mainly due to the development of drug resistance. 29 Resistance of ovarian cancer can be caused by a variety of mechanisms, including inadequate accumulation of chemotherapy drugs, inactivation of chemotherapy drugs, repair of DNA damage, and activation of…”