Abstract
ObjectivesEndometrioid carcinoma of the ovary is one of the most types of epithelial ovarian cancer associated to endometrioisis. Endometrioid tumors as well as endometriotic implants are characterized by the presence of epithelial cells, stromal cells, or a combination of booth, that resemble the endometrial cells, suggesting a possible endometrial origin of these tumors. Pro-inflammatory cytokines, including interleukin-1 (IL-1) have been reported to be involved in both endometriosis and ovarian carcinogenesis. The major objective of this study was to determine the level expression of IL-1 ligands system (IL-1α, IL-1β and IL-1RA) in the most common subtypes of ovarian cancer cells compared to endometrial cells.MethodsWe used primary endometrial cells, endometrial cell line RL-952 and different subtypes of epithelial ovarian cancer cell lines including TOV-112D (endometrioid), TOV-21G (clear cell) and OV-90 (serous). Immunofluorescence and real-time PCR analysis were used respectively for detecting IL-1 ligands at the levels of cell-associated protein and mRNA. Soluble IL-1 ligands were analyzed by ELISA.ResultsWe demonstrated that IL-1 ligands were expressed by all endometriosis-associated ovarian cancer subtypes and endometrial cells. In contrast to other cancer ovarian cells, endometrioid cells exhibit a specific decrease of cell-associated IL-1RA expression and its soluble secretion.ConclusionEndometrioid ovarian cancer exhibits an alteration in the expression of IL-1RA, a key protector against tumorogenic effects of IL-1. This alteration evokes the same alteration observed in endometriotic cells in previous studies. This suggests a possible link between the endometrium, the tissue ectopic endometriosis and endometrioid ovarian cancer.
Highlights
Ovarian cancer, the leading cause of death from gynecological malignancy, is the seventh most common malignancy in women worldwide
We demonstrated that IL-1 ligands were expressed by all endometriosis-associated ovarian cancer subtypes and endometrial cells
In contrast to other cancer ovarian cells, endometrioid cells exhibit a specific decrease of cell-associated IL-1RA expression and its soluble secretion
Summary
The leading cause of death from gynecological malignancy, is the seventh most common malignancy in women worldwide. Ovarian cancer has been reported in patients with pre-existing endometriosis, known as endometriosis-associated ovarian cancer (EAOC) [2,3]. It has been reported an increased risk of ovarian cancer in women with endometriosis [2,3]. IL-1, a major pro-inflammatory cytokine, is physiologically involved in the process of ovulation [10,11,12,13,14] and implantation [15,16]; and pathologically in epithelial ovarian carcinoma [17,18,19,20,21], endometrial tumors [9,22] and endometriosis [23]. IL-1 potentates invasiveness and metastasis of malignant cells, by inducing adhesion molecule expression on tumor as well as on the endothelial cells [24,25,26,27]
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