Expression of soluble interleukin-6 receptor in malignant ovarian tissue

• Published in: American journal of obstetrics and gynecology 2010-09, Vol.203 (3), p.230.e1-230.e8
• Main Authors: Rath, Kellie S., MD, Funk, Holly M., BSc, Bowling, Marcia C., MD, Richards, William E., MD, Drew, Angela F., PhD
• Format: Article
• Language: English
• Subjects: a disintegrin and metalloprotease domain 10; a disintegrin and metalloprotease domain 17; ADAM Proteins - metabolism; ADAM10 Protein; ADAM17 Protein; Adenocarcinoma, Clear Cell - metabolism; Adult; Aged; Amyloid Precursor Protein Secretases - metabolism; Animals; Biological and medical sciences; Cell Line, Tumor; Cystadenocarcinoma, Papillary - metabolism; Cystadenocarcinoma, Serous - metabolism; cytokine receptor; Enzyme-Linked Immunosorbent Assay; Female; Gynecology. Andrology. Obstetrics; Humans; Immunohistochemistry; inflammation; interleukin-6; Interleukin-6 - metabolism; Medical sciences; Membrane Proteins - metabolism; Mice; Middle Aged; Obstetrics and Gynecology; Ovarian Neoplasms - metabolism; ovarian tumor; Ovary - metabolism; Polymerase Chain Reaction; Protein Isoforms; Receptors, Interleukin-6 - metabolism; RNA - metabolism; Up-Regulation
• ISSN: 0002-9378; 1097-6868
• DOI: 10.1016/j.ajog.2010.03.034

Objective The objective of the study was to investigate interleukin-6 receptor (IL6R) isoforms and sheddases in the ovarian tumor microenvironment. Study Design Expression of IL6R and sheddases was measured in tissue samples of papillary serous ovarian carcinomas and benign ovaries by real-time polymerase chain reaction and immunohistochemistry. Murine xenograft samples were tested by enzyme-linked immunosorbent assay to discriminate and evaluate tumor and host contributions of IL6R. Results IL6R expression was increased in malignant ovarian tumors and localized to epithelial cells. Expression of a soluble splice variant of IL6R was increased in malignant tumors, as were the sheddases for the full-length isoform. An in vivo xenograft model showed that host IL6R expression is also increased and regulated by tumor-associated inflammation. Conclusion IL6R is overexpressed in epithelial ovarian malignancies because of increases in a soluble IL6R variant, in the sheddases for full-length IL6R and host IL6R expression. Soluble IL6R may be an efficacious target for reducing IL6-mediated ovarian tumor progression.