%0 Journal Article
%T Ovarian Epithelial-Stromal Interactions: Role of Interleukins 1 and 6
%A Kamisha T. Woolery
%A Patricia A. Kruk
%J Obstetrics and Gynecology International
%D 2011
%I Hindawi Publishing Corporation
%R 10.1155/2011/358493
%X Ovarian epithelial cancer is the most lethal gynecologic malignancy. The high mortality is attributed to the fact that most cases typically present in late stage when ovarian cancer (OC) has already spread beyond the ovary. Ovarian epithelial cancer cells are shed into intraperitoneal ascites and easily disseminate throughout the peritoneal cavity with preferential metastasis to the omentum, peritoneum, and local organs. Understanding how ovarian epithelial cells interact with and modulate their microenvironment can provide insight into the molecular mechanism(s) involved with malignant transformation and progression which may eventually identify novel diagnostic, prognostic, and therapeutic targets. The objective of this paper is to provide a brief consideration of ovarian surface epithelial-stromal interactions in regard to normal physiological function and tumor progression as influenced by two potentially key interleukins, interleukins-1 (IL-1) and -6 (IL-6), present in the microenvironment. Lastly, we will consider the clinical implications of IL-1 and IL-6 for OC patients. 1. Introduction Ovarian cancer (OC) is the leading cause of gynecologic cancer death in women in the US. It is the fourth leading cause of cancer death among women after lung, breast, and colorectal cancer and is associated with a 1.7% lifetime risk [1¨C4]. It is estimated that 23,100 new cases are diagnosed in the US annually [4] and that 14,000 women die annually from this disease. The one-year survival rate for OC can be as high as 79% and when diagnosed in an early stage the 5-year survival rate is almost 95% [4]. However, when diagnosed at a later stage, the 5-year survival is generally no better than 35% [4]. Optimal cytoreduction followed by platinum-based chemotherapy remains the mainstay of therapy in the management of advanced epithelial ovarian cancers [2]. However, while the response rate to primary chemotherapy can be as high as 76%, response rate is dramatically reduced after relapse of disease [5]. Platinum resistance, defined as disease recurrence less than six months from completion of therapy, is an important prognostic predictor. Patients with platinum-resistant tumors have a response rate of less than 10% when retreated with platinum compounds [6, 7] and alternative options also have poor response rates of 18¨C30% [8¨C15]. Ovarian surface epithelium-(OSE-) derived tumors account for 90% of malignant ovarian tumors with serous tumors accounting for over 30% of all OSE-derived cancers [16]. The majority of ovarian cancers are sporadic in origin, but about 10% of
%U http://www.hindawi.com/journals/ogi/2011/358493/