Interleukin-11 receptor expression in primary ovarian carcinomas.
OBJECTIVE
The objectives of this study were to determine (1) the frequency of expression of the interleukin-11 receptor alpha subunit (IL-11Ralpha) and its signal transducing subunit, gp130, among primary ovarian carcinomas; (2) the frequency of expression of IL-11 in ovarian carcinomas; and (3) the potential role IL-11 might have in ovarian cancer cell biology.


METHODS
An immunohistochemical assay was used to determine the expression of IL-11Ralpha and the gp130 cofactor among primary ovarian carcinomas; the expression of IL-11 in ovarian malignancies was determined using reverse transcription polymerase chain reaction (RT-PCR). The ability of IL-11 to stimulate [3H]thymidine incorporation in IL-11R-expressing ovarian carcinoma cell lines (OVCAR-3 and SKOV-3) and/or abrogate cell death mediated by apoptosis-inducing agents using an ELISA assay that quantitates DNA fragmentation was also studied.


RESULTS
IL-11Ralpha was expressed in the malignant epithelial cells of 45 of 48 (93.8%) primary ovarian carcinoma samples studied. In 45 primary ovarian carcinoma samples where both components of the IL-11 receptor (IL-11Ralpha and gp130) were examined, coexpression was observed in 42 (93.3%). Expression of the IL-11 receptor components was also found in the stromal layer. Coexpression of IL-11Ralpha and gp130 was commonly observed in both benign ovarian tumors and in the epithelial layer of normal ovaries. In contrast, IL-11 mRNA was expressed in only 3 of 21 malignant samples studied (14.3%). Recombinant human IL-11 was unable either to stimulate [3H]thymidine incorporation or to block cell death effected by paclitaxel or Fas-activating antibodies in in vitro assays using OVCAR -3 or SKOV-3 cells.


CONCLUSIONS
The IL-11 receptor system is commonly expressed in both malignant and nonmalignant ovarian tissues, although its function in ovarian epithelial cell biology remains unclear.
Campbell
C L
CL
Cytokine/Cytokine Receptor Laboratory, LINK Laboratories, UMASS Cancer Center, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
Guardiani
R
R
Ollari
C
C
Nelson
B E
BE
Quesenberry
P J
PJ
Savarese
T M
TM
D015703:Antigens, CD / Q000096:biosynthesis; D050822:Cytokine Receptor gp130; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017370:Interleukin-11 / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology; D053703:Interleukin-11 Receptor alpha Subunit; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D010053:Ovary / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018123:Receptors, Interleukin / Q000096:biosynthesis* / Q000235:genetics; D053702:Receptors, Interleukin-11; D011994:Recombinant Proteins / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; C508428:IL11RA protein, human; C494199:IL6ST protein, human; D017370:Interleukin-11; D053703:Interleukin-11 Receptor alpha Subunit; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053702:Receptors, Interleukin-11; D011994:Recombinant Proteins; D050822:Cytokine Receptor gp130