Ovarian Cancer Stem Cells: Characterization and Role in Tumorigenesis

Abstract

Ovarian cancer is a heterogenous disease with variable clinicopathological and molecular mechanisms being responsible for tumorigenesis. Despite substantial technological improvement, lack of early diagnosis contributes to its highest mortality. Ovarian cancer is considered to be the most lethal female gynaecological cancer across the world. Conventional treatment modules with platinum- and Taxane-based chemotherapy can cause an initial satisfactory improvement in ovarian cancer patients. However, approximately 75–80% patients of advanced stage ovarian cancer, experience relapse and nearly 40% have overall poor survival rate. It has been observed that a subpopulation of cells referred as cancer stem cells (CSCs), having self renewal property, escape the conventional chemotherapy because of their quiescent nature. Later, these CSCs following its interaction with microenvironment and release of various inflammatory cytokines, chemokines and matrix metalloproteinases, induce invasion and propagation to distant organs of the body mainly peritoneal cavity. These CSCs can be enriched by their specific surface markers such as CD44, CD117, CD133 and intracellular enzyme such as aldehyde dehydrogenase. This tumorigenicity is further aggravated by the epithelial to mesenchymal transition of CSCs and neovascularisation via epigenetic reprogramming and over-expression of various signalling cascades such as Wnt/β-catenin, NOTCH, Hedgehog, etc. to name a few. Hence, a comprehensive understanding of various cellular events involving interaction between cancer cells and cancer stem cells as well as its surrounding micro environmental components would be of unmet need to achieve the ultimate goal of better management of ovarian cancer patients. This chapter deals with the impact of ovarian cancer stem cells in tumorigenesis which would help in the implementation of basic research into the clinical field in the form of translational research in order to reduce the morbidity and mortality in ovarian cancer patients through amelioration of diagnosis and impoverishment of therapeutic resistance.