Expression of soluble interleukin-6 receptor in malignant ovarian tissue.
OBJECTIVE
The objective of the study was to investigate interleukin-6 receptor (IL6R) isoforms and sheddases in the ovarian tumor microenvironment.


METHODS
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.


CONCLUSIONS
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.
Rath
Kellie S
KS
Department of Cancer and Cell Biology, University of Cincinnati School of Medicine, Cincinnati, OH, USA.
Funk
Holly M
HM
Bowling
Marcia C
MC
Richards
William E
WE
Drew
Angela F
AF
D051722:ADAM Proteins / Q000378:metabolism; D000072197:ADAM10 Protein; D000072198:ADAM17 Protein; D018262:Adenocarcinoma, Clear Cell / Q000378:metabolism; D000328:Adult; D000368:Aged; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D018283:Cystadenocarcinoma, Papillary / Q000378:metabolism; D018284:Cystadenocarcinoma, Serous / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D015850:Interleukin-6 / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000378:metabolism*; D010053:Ovary / Q000378:metabolism; D016133:Polymerase Chain Reaction; D020033:Protein Isoforms; D012313:RNA / Q000378:metabolism; D019947:Receptors, Interleukin-6 / Q000378:metabolism*; D015854:Up-Regulation
D015850:Interleukin-6; D008565:Membrane Proteins; D020033:Protein Isoforms; D019947:Receptors, Interleukin-6; D012313:RNA; D053829:Amyloid Precursor Protein Secretases; D051722:ADAM Proteins; D000072197:ADAM10 Protein; C491236:ADAM10 protein, human; D000072198:ADAM17 Protein