1. ¹Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT, USA
2. ²Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA

Correspondence: Dr G Mor, Reproductive Immunology Unit, Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, 333 Cedar Street FMB 301, New Haven, CT 06520, USA. E-mail: Gil.Mor@yale.edu

Received 26 November 2007; Revised 24 January 2008; Accepted 4 March 2008; Published online 14 April 2008.

Abstract

Cancer progression is an abnormal form of tissue repair characterized by chronic inflammation. IB kinase- (IKK) required for nuclear factor-B (NF-B) activation plays a critical role in this process. Using EOC cells isolated from malignant ovarian cancer ascites and solid tumors, we identified IKK as a major factor promoting a functional TLR–MyD88–NF-B pathway that confers to EOC cell the capacity to constitutively secrete proinflammatory/protumor cytokines and therefore promoting tumor progression and chemoresistance. Furthermore, we describe for the first time the identification of the microRNA hsa-miR-199a as a regulator of IKK expression. Our study describes the property of ovarian cancer cells to enhance the inflammatory microenvironment as a result of the expression of an active IKK pathway. Identification of these markers in patients' tumor samples may facilitate the adequate selection of treatment and open new venues for the development of effective therapy for chemoresistant ovarian cancers.