title: Interleukin-30 expression in prostate cancer and its draining lymph nodes correlates with advanced grade and stage.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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
  We provide 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.
authors.affiliation: Authors' Affiliations: Department of Medicine and Sciences of Aging, Section of Anatomic Pathology and Molecular Medicine; Ce.S.I. Aging Research Center, "G. d'Annunzio" University Foundation, Chieti; and Laboratory of Oncology, Istituto Giannina Gaslini, Genova, Italy.
authors.forename: Serena
authors.initials: S
authors.lastname: Di Meo
authors.forename: Irma
authors.initials: I
authors.lastname: Airoldi
authors.forename: Carlo
authors.initials: C
authors.lastname: Sorrentino
authors.forename: Alessia
authors.initials: A
authors.lastname: Zorzoli
authors.forename: Silvia
authors.initials: S
authors.lastname: Esposito
authors.forename: Emma
authors.initials: E
authors.lastname: Di Carlo
mesh_terms: D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007378:Interleukins / Q000096:biosynthesis*; D061346:Laser Capture Microdissection; D008198:Lymph Nodes / Q000378:metabolism* / Q000473:pathology; D008207:Lymphatic Metastasis / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D007378:Interleukins; C464565:MYDGF protein, human