Recent Advancements in the Field of Ovarian Cancer Stem Cells
Moorthy P. Ponnusamy, PhD Parthasarathy Seshacharyulu, PhD Surinder K. Batra, PhD
Origin and Current Views on Cancer Stem Cells
Ovarian cancer is a highly lethal disease which represents a great clinical challenge in gynecologic oncology. It is one of the most challenging of all cancers to fight as it often goes undiagnosed until it has already advanced and metastasized. The current therapeutic strategies have been inefficient and tumor recurrence is observed in up to 70% of patients with advanced stage ovarian cancer after treatment. The major limiting factor in the treatment of ovarian cancer is recurrence and chemoresistance. Tumors contain cells which are heterogeneous in nature at both the cellular and molecular levels, containing stem-like tumor initiating cells known as cancer stem cells (CSC). These cancer stem cells or tumor initiating cells have the ability to self-renew. This self-renewal is responsible for the disease aggressiveness, metastasis and resistance to therapy. The identification of cancer stem cells through stem cell characteristics might have a relevant clinical implication. The overall characterization and biology of ovarian cancer stem cells (Figure 1) were described in this chapter.
Stem cells are undifferentiated cells capable of self-renewal which undergo asymmetric division giving rise to differentiated progenitor cells (Blau et al. 2001). Accumulating evidence has shown that there is an increase in the proliferative rate of stem cells in response to injury (Forge et al., 1993). Recently, it has been discovered that stem cells have the ability to be transported from one or various tissues to distant organ/sites during the process of tumor pathogenesis, which has long been recognized as a characteristic of metastatic cancer cells. Indeed, a well developed model of cancer cell metastasis proposes that only a rare subset of cells, probably the cancer stem cells, are responsible for this phenotype (Reya et al. 2001). Most recently, much attention has been focused on the role of cancer stem cells in the formation, propagation and progression of various tumors. However identification of the cancer stem cells has remained elusive, as the CSCs are usually asymptomatic and identified only at a later stage. Cancer stem cells, like somatic stem cells, are thought to be capable of self-renewal and originate from normal stem cells, progenitor cells and differentiated cancer cells (Figure 2). The
Figure 1. Schematic representation of the overall view of cancer stem cells. It explains the clinical importance and signaling pathways for cancer stem cells: 1) Properties of cancer stem cells explain CSC differentiation, self-renewal, origin of CSC, source of CSC and targets for CSC; 2) Clinical implications of CSC including drug treatment, drug resistance and tumor relapse; 3) Signaling pathway for CSC maintenance such as Notch, Wnt/ β-catenin and Sonic hedgehog; and 4) Finally, the recent advanced questions for CSCs.
u Recent Advancements in the Field of Ovarian Cancer Stem Cells
Current Status of Ovarian Cancer and Ovarian CSCs (OCSCs)
Figure 2. Diagrammatic illustration explains the origin of specific ovarian cancer stem cells from ovarian surface epithelium (OSE) and its transformation.
most widely accepted hypothesis is that cancers are driven by a subset of highly tumorigenic cells (