Cytokine profiling of prostatic fluid from cancerous prostate glands identifies cytokines associated with extent of tumor and inflammation

被引:45
作者
Fujita, Kazutoshi [1 ]
Ewing, Charles M. [1 ]
Sokoll, Lori J. [1 ,2 ]
Elliott, Debra J. [1 ,2 ]
Cunningham, Mark [1 ]
De Marzo, Angelo M. [1 ,2 ]
Isaacs, William B. [1 ]
Pavlovich, Christian P. [1 ]
机构
[1] Johns Hopkins Med Inst, James Buchanan Brady Urol Inst, Baltimore, MD 21205 USA
[2] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA
关键词
cancer; inflammation; cytokine;
D O I
10.1002/pros.20755
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
BACKGROUND. Cytokines are key mediators of inflammation that may relate to Prostate cancer initiation and progression, and that may be useful markers of prostatic neoplasia and related inflammation. In order to better understand the relationship between cytokines and prostate cancer, we profiled cytokines in prostatic fluids obtained from cancerous prostate glands and correlated them to both cancer status and inflammatory grade. METHODS. Prostatic fluid was collected from fresh radical prostatectomy specimens and analyzed by cytokine antibody microarray. For comparison, cases were selected from patients with either minimal or extensive cancer volume on final pathology. Among the cytokines with the greatest difference between the tumor volume groups, eight had their levels quantitated by ELISA. In addition, the grade of prostatic inflammation by neutrophils, macrophages and lymphocytes was scored for each case and examined for correlations with cytokine levels. RESULTS. Among 174 cytokines analyzed, HGF was the most increased (6.57-fold), and along with IL18Bpa was significantly elevated in patients with extensive disease compared to those with minimal disease. IL17, GITR, and ICAM-1 were elevated in specimens with significant neutrophilic inflammation into gland lumina, and IL1813pa, 11,17, GITR, and ICAM-1 were elevated in specimens with significant lymphocytic inflammation in prostatic stroma. CONCLUSIONS. Prostatic fluid cytokines were identified that may be useful for early cancer detection and prognostication efforts and for assessment of prostatic inflammation, particularly if they can be found not only in prostatic fluids obtained ex vivo, but in expressed prostatic secretions or urine samples from men with prostates still in situ.
引用
收藏
页码:872 / 882
页数:11
相关论文
共 37 条
[1]   ADHESION MOLECULES AND INFLAMMATORY INJURY [J].
ALBELDA, SM ;
SMITH, CW ;
WARD, PA .
FASEB JOURNAL, 1994, 8 (08) :504-512
[2]   Correlation of minute (0.5 mm or less) focus of prostate adenocarcinoma on needle biopsy with radical prostatectomy specimen: Role of prostate specific antigen density [J].
Allan, RW ;
Sanderson, H ;
Epstein, JI .
JOURNAL OF UROLOGY, 2003, 170 (02) :370-372
[3]   Cross-talk between paracrine-acting cytokine and chemokine pathways promotes malignancy in benign human prostatic [J].
Ao, Mingfang ;
Franco, Omar E. ;
Park, Dean ;
Raman, Dayanidhi ;
Williams, Karin ;
Hayward, Simon W. .
CANCER RESEARCH, 2007, 67 (09) :4244-4253
[4]   Epithelial-neutrophil activating peptide (ENA-78) is an important angiogenic factor in non-small cell lung cancer [J].
Arenberg, DA ;
Keane, MP ;
DiGiovine, B ;
Kunkel, SL ;
Morris, SB ;
Xue, YY ;
Burdick, MD ;
Glass, MC ;
Iannettoni, MD ;
Strieter, RM .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 102 (03) :465-472
[5]   Cancer immunoediting by GITR (glucocorticoid-induced TNF-related protein) ligand in humans: NK cell/tumor cell interactions [J].
Baltz, Katrin M. ;
Krusch, Matthias ;
Bringmann, Anita ;
Brossart, Peter ;
Mayer, Frank ;
Kloss, Mercedes ;
Baessler, Tina ;
Kumbier, Ingrid ;
Peterfi, Andrea ;
Kupka, Susan ;
Kroeber, Stefan ;
Menzel, Dagmar ;
Radsak, Markus P. ;
Rammensee, Hans-Georg ;
Salih, Helmut R. .
FASEB JOURNAL, 2007, 21 (10) :2442-2454
[6]   Natural regulatory T cells in infectious disease [J].
Belkaid, Y ;
Rouse, BT .
NATURE IMMUNOLOGY, 2005, 6 (04) :353-360
[7]   Regulatory T cells in cancer [J].
Beyer, Marc ;
Schultze, Joachim L. .
BLOOD, 2006, 108 (03) :804-811
[8]   Propionibacterium acnes associated with inflammation in radicial prostatectomy specimens:: A possible link to cancer evolution? [J].
Cohen, RJ ;
Shannon, BA ;
McNeal, JE ;
Shannon, T ;
Garrett, KL .
JOURNAL OF UROLOGY, 2005, 173 (06) :1969-1974
[9]   Interleukin-12 in anti-tumor immunity and immunotherapy [J].
Colombo, MP ;
Trinchieri, G .
CYTOKINE & GROWTH FACTOR REVIEWS, 2002, 13 (02) :155-168
[10]   Role of glucocorticoid-induced TNF receptor family gene (GITR) in collagen-induced arthritis [J].
Cuzzocrea, S ;
Ayroldi, E ;
Di Paola, R ;
Agostini, M ;
Mazzon, E ;
Bruscoli, S ;
Genovese, T ;
Ronchetti, S ;
Caputi, AP ;
Riccardi, C .
FASEB JOURNAL, 2005, 19 (10) :1253-1265