Ectoenzymes in Epithelial Ovarian Carcinoma: Potential Diagnostic Markers and Therapeutic Targets

Ovarian cancer is one of the most lethal among the gynaecological malignancies, affecting 12% of women in developed countries (Cannistra, 2004). The lethality of ovarian cancer is primarily attributable to our current inability to detect the disease at an early stage, when it is still limited to the ovary. Therefore, the majority of patients are diagnosed when they have advanced-stage disease. Despite progresses in cytotoxic therapies, only 30% of patients with advanced-stage ovarian cancer survive 5 years after diagnosis. The insidious nature of ovarian cancer stems from its unique biological behaviour: ovarian carcinoma can spread by direct extension to adjacent organs, and exfoliated tumour cells can be transported in peritoneal fluid (Naora et al., 2005). Subsequent implants are characterised by their adhesion to mesothelial cells, migration throughout and invasion of the tumor cells into the omentum and peritoneum. This seeding of the peritoneal cavity is frequently associated with ascites formation. Only secondarily and rather late during the disease progression, are pelvic and para-aortic lymph nodes involved. However, the local peritoneal disease cannot be controlled and remains a factor leading to death (Feki et al., 2009). The cellular processes that lead to local and distant dissemination of ovarian cancer are not fully understood, and the mechanisms of interaction between cancer cells and mesothelium need to be further elucidated to achieve novel information on the biology of this highly aggressive form of cancer and possibly, to identify new potential targets for selective therapeutic strategies. The combined effort of clinicians and researchers has led to the identification of a number of molecules that might facilitate screening, diagnosis, prognosis and monitoring response to treatment or relapse during follow-up. These new molecules might provide specific targets for anti-tumour therapy with antibody-directed treatments, gene therapy or specific inhibitory molecules. An unexpectedly high number of these newly identified molecules have turned out to be cell surface-expressed ectoenzymes. Ectoenzymes are a large, heterogeneous class of membrane proteins whose catalytically active sites face the extracellular environment. The products of their catalytic activities can influence the extracellular environment (for example, several of these products can function as second messengers or regulate the recruitment of cells). Moreover, many ectoenzymes can function