Human breast tumor cells express IL-10 and IL-12p40 transcripts and proteins, but do not produce IL-12p70.
IL-10 transcripts were expressed in 14/15 primary breast adenocarcinomas and in 5/8 established breast tumor lines. Immunohistochemistry and immunoprecipitation from lysates and supernatants revealed that established breast tumor lines produced IL-10 protein. Immunohistochemistry revealed that IL-10 is localized to tumor cells of primary breast adenocarcinomas and to occasional infiltrating MNC. Established breast tumor cell lines expressed IL-12p40 transcripts (6/8) and protein (4/7) and IL-12p35 transcripts (6/7). Using two sandwich ELISAs, specific, respectively, for IL-12p40 and IL-12p70 proteins, we demonstrated that established breast tumor cell lines produce IL-12p40 monomer/homodimer, but not IL-12p70. Positive staining for IL-12p70 in primary breast adenocarcinomas was found only in MNC infiltrating the tumor while tumor cells were negative. IL-12p40 homodimer/monomer inhibit as antagonists IL-12 or IL-23, although they may also act as agonists and positive regulators. Also, primary breast adenocarcinomas (15/15) and established breast tumor cell lines (6/8) expressed TGF-β1 transcripts. IL-10, IL-12p40 and TGF-β1 may inhibit substantially the anti-tumor immune response.
Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, PA 19140, USA.
Mark C
MC
Heckel
Alexey
A
Wolfson
Christopher A
CA
Slachta
Roland
R
Schwarting
Padmini
P
Salgame
Christos D
CD
Katsetos
Chris D
CD
Platsoucas
D000230:Adenocarcinoma / Q000276:immunology* / Q000378:metabolism; D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000276:immunology* / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000032:analysis / Q000096:biosynthesis*; D053765:Interleukin-12 Subunit p35 / Q000032:analysis / Q000096:biosynthesis; D053762:Interleukin-12 Subunit p40 / Q000032:analysis / Q000096:biosynthesis*; D053759:Interleukin-23 / Q000819:agonists / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008875:Middle Aged; D053773:Transforming Growth Factor beta1 / Q000032:analysis / Q000276:immunology
D053765:Interleukin-12 Subunit p35; D053762:Interleukin-12 Subunit p40; D053759:Interleukin-23; D053773:Transforming Growth Factor beta1; D016753:Interleukin-10