TY - JOUR
T1 - Interleukin-30 expression in prostate cancer and its draining lymph nodes correlates with advanced grade and stage
AU - Di Meo, Serena
AU - Airoldi, Irma
AU - Sorrentino, Carlo
AU - Zorzoli, Alessia
AU - Esposito, Silvia
AU - Di Carlo, Emma
PY - 2014
Y1 - 2014
N2 - Purpose: The interleukin (IL)-27 cytokine subunit p28, also called IL-30, has been recognized as a novel immunoregulatory mediator endowed with its own functions. These are currently the subject of discussion in immunology, but completely unexplored in cancer biology. We set out to investigate the role of IL-30 in prostate carcinogenesis and its effects on human prostate cancer (hPCa) cells. Experimental Design: IL-30 expression, as visualized by immunohistochemistry and real-time reverse transcriptase PCR on prostate and draining lymph nodes from 125 patients with prostate cancer, was correlated with clinicopathologic data. IL-30 regulation of hPCa cell viability and expression of selected gene clusters was tested by flow cytometry and PCR array. Results: IL-30, absent in normal prostatic epithelia, was expressed by cancerous epithelia with Gleason ≥ 7%of 21.3% of prostate cancer stage I to III and 40.9% of prostate cancer stage IV. IL-30 expression by tumor infiltrating leukocytes (T-ILK) was higher in stage IV that in stage I to III prostate cancer (P = 0.0006) or in control tissue (P=0.0011). IL-30 expression in prostate draining lymph nodes (LN)-ILK was higher in stage IV than in stage I to III prostate cancer (P=0.0031) or in control nodes (P=0.0023). The main IL-30 sources were identified as CD68 + macrophages, CD33 + /CD11b + myeloid cells, and CD14 + monocytes. In vitro, IL- 30 stimulated proliferation of hPCa cells and also downregulated CCL16/LEC, TNFSF14/LIGHT, chemokine- like factor (CKLF), and particularly CKLF-like MARVEL transmembrane domain containing 3 (CMTM3) and greatly upregulated ChemR23/CMKLR. Conclusions:Weprovide the first evidence that IL-30 is implicated in prostate cancer progression because (i) its expression by prostate cancer or T- and LN-ILK correlates with advanced disease grade and stage; and (ii) IL-30 exerts protumor activity in hPCa cells.
AB - Purpose: The interleukin (IL)-27 cytokine subunit p28, also called IL-30, has been recognized as a novel immunoregulatory mediator endowed with its own functions. These are currently the subject of discussion in immunology, but completely unexplored in cancer biology. We set out to investigate the role of IL-30 in prostate carcinogenesis and its effects on human prostate cancer (hPCa) cells. Experimental Design: IL-30 expression, as visualized by immunohistochemistry and real-time reverse transcriptase PCR on prostate and draining lymph nodes from 125 patients with prostate cancer, was correlated with clinicopathologic data. IL-30 regulation of hPCa cell viability and expression of selected gene clusters was tested by flow cytometry and PCR array. Results: IL-30, absent in normal prostatic epithelia, was expressed by cancerous epithelia with Gleason ≥ 7%of 21.3% of prostate cancer stage I to III and 40.9% of prostate cancer stage IV. IL-30 expression by tumor infiltrating leukocytes (T-ILK) was higher in stage IV that in stage I to III prostate cancer (P = 0.0006) or in control tissue (P=0.0011). IL-30 expression in prostate draining lymph nodes (LN)-ILK was higher in stage IV than in stage I to III prostate cancer (P=0.0031) or in control nodes (P=0.0023). The main IL-30 sources were identified as CD68 + macrophages, CD33 + /CD11b + myeloid cells, and CD14 + monocytes. In vitro, IL- 30 stimulated proliferation of hPCa cells and also downregulated CCL16/LEC, TNFSF14/LIGHT, chemokine- like factor (CKLF), and particularly CKLF-like MARVEL transmembrane domain containing 3 (CMTM3) and greatly upregulated ChemR23/CMKLR. Conclusions:Weprovide the first evidence that IL-30 is implicated in prostate cancer progression because (i) its expression by prostate cancer or T- and LN-ILK correlates with advanced disease grade and stage; and (ii) IL-30 exerts protumor activity in hPCa cells.
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U2 - 10.1158/1078-0432.CCR-13-2240
DO - 10.1158/1078-0432.CCR-13-2240
M3 - Article
C2 - 24277453
AN - SCOPUS:84893495713
VL - 20
SP - 585
EP - 594
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 3
ER -