Role of Stem Cells in Metastasis in Ovarian Cancer
Role of Stem Cells in Metastasis in Ovarian Cancer
mahdieh balavar,1,*
1. BA student, Tehran, Azad University, Shahr Ray branch
Introduction: Ovarian cancer with 22,240 new cases reported in the United States each year, ovarian cancer (OC) is the most common cause of mortality from gynecologic malignancies. Metastasis is a common problem in OC treatment because it is believed that 75% of OC patients had disseminated illness in the peritoneal cavity at the time of initial diagnosis. Although this treatment is initially successful, the five-year survival rate is only about 30% and up to 80% of women with advanced-stage ovarian high-grade serous carcinoma (HGSOC) relapse with metastatic cancer. According to the CSC theory, a subset of malignant cells exists within a tumor that is more likely to self-renew, produce a variety of tumour-related cells, and support carcinogenesis. The aim of this study was to investigate the Role of Stem Cells in Metastasis in Ovarian Cancer.
Methods: This review study has been written from scientific databases such as Science Direct, Springer, Google Scholar, and PubMed.
Results: Multiple studies have shown ascites to be a rich source of OCSCs. This non-adherent microenvironment is lethal to adherent tumors cells, and only cells with mesenchymal features can tolerate the anoikis stress and survive. Ascites contains a variety of tumour-promoting soluble factors that contribute to CSC enrichment, such as interleukin (IL)-6, IL-8, IL-10, osteoprotegerin, vascular endothelial growth factor (VEGF), and extracellular vehicles (EVs) . We recently reported that IL-6 regulates stemness features of CSCs by activating STAT3 signaling and enhancing ALDH1A1 expression. In addition, several studies have emphasized the importance of EVs in promoting cancer progression, which adds another level of complexity to study the microenvironment of ascites. Runz and colleagues identified CD24 and EpCAM as cargo proteins of exosomes in cell lines and malignant ascites, which are both stemness and prognostic markers of OC. Other molecules carried by EVs reported in OC include L1 adhesion molecule (CD171), activated leukocyte cell adhesion molecule (ALCAM), CD44 and claudin-4. Given the variety of potential factors contributing to CSC maintenance, ascites is considered to promote the acquisition of the stem cell state. Floating OC cells travel along with the ascites, with the movement of respiratory force, before settling onto the new sites. Adhesion to mesothelium, the lining of the peritoneal cavity, is the first step of implantation. This step is facilitated by CD44 and β1 integrin heterodimers on the surface of floating OC cells, which are ligands for hyaluronic acid (HA) and the extracellular matrix molecules on mesothelial cells. Intriguingly, mesothelial cells facilitate cancer stemness properties in spheroids of OC cells, including increasing CD44 expression, suggesting a positive feedback loop in the adhesion step between mesothelium and floating OC cells.
Conclusion: It is notable that the CSC population within a tumor is not a uniform collection of cells. Cell division is made possible by the asymmetric division that distinguishes CSCs. Additionally, the dynamic coexistence of CSC in quiescent, proliferative, and metastatic phases may activate several signaling pathways, leading to therapy failure with a single conventional treatment. In order to address heterogeneity, a recent study developed patient-derived OC organoid culture systems. Organoid lines were xenografted to the main tumor to capture the intratumoral and intertumoral heterogeneity of the tumor. This cutting-edge technology has a lot of potential for customized OCSC-based therapeutics. Another obstacle is the small therapeutic window that results from CSC-directed therapy's lack of specificity compared to regular stem cells. For instance, it has been demonstrated that blocking BET has an impact on intestinal stem cells, resulting in GI toxicity and a disruption of tissue homeostasis in numerous organs. Target selection is required due to biological distinctions between CSCs and regular stem cells that prevent off-target effects. A more effective intervention would be made possible by significant developments in delivery technologies, such as the use of nanoparticle-mediated strategies and oncolytic viruses that only multiply in cancer cells. Together, minimizing side effects related to targeted therapy and enhancing pharmacological efficacy are crucial. The creation of the ideal timing for administering CSC-targeted treatment and the emergence of resistance are additional difficulties. The greatest benefit to patients may come through early CSC intervention, either prior to or concurrently administered with chemotherapy.