Immunohistochemical analysis of the IL-6 family of cytokines and their receptors in benign, hyperplasic, and malignant human prostate.
Interleukin-6 (IL-6) and its receptor have been implicated in prostate cancer progression. Because other members of the IL-6 family such as leukaemia inhibitory factor (LIF) and oncostatin M (OSM) share gp130, the signal transduction subunit of their receptors, interpretation of the data without considering the expression of these cytokines and their specific receptor subunits could be misleading. The immunohistochemical pattern of the IL-6 family and their receptor subunits in normal prostate, benign prostatic hyperplasia (BPH), and prostatic carcinoma (PC) was investigated. In normal prostates, gp130 and OSMRalpha were detected exclusively in the stroma and LIFRbeta was very scarce. While IL-6 was scarcely immunolocalized to the basal cells of the epithelium, OSM was detected in the stroma and LIF in both the epithelium and the stroma. This suggests an autocrine role for this family of cytokines in the stroma of normal prostates. In BPH, gp130 and OSMRalpha were detected both in the epithelium and in the stroma, whereas LIFRbeta was localized only to the epithelium. IL-6 localized preferentially to the epithelium, OSM to the stroma, and LIF to both compartments. Therefore, in addition to the autocrine role in the stroma, IL-6 and OSM may play a paracrine role from the stroma to the epithelium in BPH. In PC, gp130 and OSMRalpha were detected both in the epithelium and in the stroma, increasing with rising Gleason grade, whereas LIFRbeta was localized exclusively to the epithelium of low Gleason grade carcinomas. IL-6, LIF, and OSM localized in all cell types, with immunostaining increasing with Gleason grade. These data suggest an autocrine role for these cytokines in the epithelial cells of PC. The distinct pattern of expression of LIFRbeta exclusively in low Gleason grade carcinomas makes LIFRbeta a candidate for malignancy diagnosis. The role of OSM mainly in high Gleason grade carcinomas makes OSM a putative target for prostate cancer therapy.
Royuela
Mar
M
Department of Cell Biology and Genetics, University of Alcala, Madrid, Spain.
Ricote
Monica
M
Parsons
Melanie S
MS
García-Tuñón
Ignacio
I
Paniagua
Ricardo
R
de Miguel
Maria P
MP
D000368:Aged; D000369:Aged, 80 and over; D015703:Antigens, CD / Q000032:analysis; D015153:Blotting, Western / Q000379:methods; D050822:Cytokine Receptor gp130; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D015850:Interleukin-6 / Q000032:analysis*; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis; D008875:Middle Aged; D053683:Oncostatin M; D010455:Peptides / Q000032:analysis; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D018121:Receptors, Cytokine / Q000032:analysis; D019947:Receptors, Interleukin-6 / Q000032:analysis*; D053606:Receptors, OSM-LIF; D053677:Receptors, Oncostatin M; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D015398:Signal Transduction; D017154:Stromal Cells / Q000378:metabolism
D015703:Antigens, CD; C494199:IL6ST protein, human; D015850:Interleukin-6; C507837:LIF protein, human; C507840:LIFR protein, human; D053605:Leukemia Inhibitory Factor; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit; D008562:Membrane Glycoproteins; C508351:OSM protein, human; D010455:Peptides; D018121:Receptors, Cytokine; D019947:Receptors, Interleukin-6; D053606:Receptors, OSM-LIF; D053677:Receptors, Oncostatin M; D053683:Oncostatin M; D050822:Cytokine Receptor gp130