Myofibroblast-Derived SFRP1 as Potential Inhibitor of Colorectal Carcinoma Field Effect

被引:35
作者
Valcz, Gabor [1 ]
Patai, Arpad V. [2 ]
Kalmar, Alexandra [2 ]
Peterfia, Balint [2 ]
Furi, Istvan [2 ]
Wichmann, Barnabas [1 ]
Muzes, Gyoergyi [2 ]
Sipos, Ferenc [2 ]
Krenacs, Tibor [3 ]
Mihaly, Emese [2 ]
Spisak, Sandor [4 ]
Molnar, Bela [1 ,2 ]
Tulassay, Zsolt [1 ,2 ]
机构
[1] Hungarian Acad Sci, Mol Med Res Unit, Budapest, Hungary
[2] Semmelweis Univ, Dept Internal Med 2, H-1085 Budapest, Hungary
[3] Semmelweis Univ, Dept Pathol & Expt Canc Res 1, H-1085 Budapest, Hungary
[4] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA
关键词
FRIZZLED-RELATED PROTEIN-1; WNT SIGNALING PATHWAY; BETA-CATENIN; COLON-CANCER; PROMOTER METHYLATION; WNT/BETA-CATENIN; GENES; EXPRESSION; CELLS; BINDS;
D O I
10.1371/journal.pone.0106143
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Epigenetic changes of stromal-epithelial interactions are of key importance in the regulation of colorectal carcinoma (CRC) cells and morphologically normal, but genetically and epigenetically altered epithelium in normal adjacent tumor (NAT) areas. Here we demonstrated retained protein expression of well-known Wnt inhibitor, secreted frizzled-related protein 1 (SFRP1) in stromal myofibroblasts and decreasing epithelial expression from NAT tissues towards the tumor. SFRP1 was unmethylated in laser microdissected myofibroblasts and partially hypermethylated in epithelial cells in these areas. In contrast, we found epigenetically silenced myofibroblast-derived SFRP1 in CRC stroma. Our results suggest that the myofibroblast-derived SFRP1 protein might be a paracrine inhibitor of epithelial proliferation in NAT areas and loss of this signal may support tumor proliferation in CRC.
引用
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页数:8
相关论文
共 45 条
[1]   WNT signalling pathways as therapeutic targets in cancer [J].
Anastas, Jamie N. ;
Moon, Randall T. .
NATURE REVIEWS CANCER, 2013, 13 (01) :11-26
[2]   Field defects in progression to gastrointestinal tract cancers [J].
Bernstein, Carol ;
Bernstein, Harris ;
Payne, Claire M. ;
Dvorak, Katerina ;
Garewal, Harinder .
CANCER LETTERS, 2008, 260 (1-2) :1-10
[3]   Beyond Wnt inhibition: new functions of secreted Frizzled-related proteins in development and disease [J].
Bovolenta, Paola ;
Esteve, Pilar ;
Ruiz, Jose Maria ;
Cisneros, Elsa ;
Lopez-Rios, Javier .
JOURNAL OF CELL SCIENCE, 2008, 121 (06) :737-746
[4]  
Braakhuis BJM, 2003, CANCER RES, V63, P1727
[5]   Wnt breakers in colon cancer [J].
Clevers, H .
CANCER CELL, 2004, 5 (01) :5-6
[6]   Wnt/β-Catenin Signaling and Disease [J].
Clevers, Hans ;
Nusse, Roel .
CELL, 2012, 149 (06) :1192-1205
[7]   c-Myc transforms human mammary epithelial cells through repression of the Wnt inhibitors DKK1 and SFRP1 [J].
Cowling, Victoria H. ;
D'Cruz, Celina M. ;
Chodosh, Lewis A. ;
Cole, Michael D. .
MOLECULAR AND CELLULAR BIOLOGY, 2007, 27 (14) :5135-5146
[8]   Frequent loss of SFRP1 expression in multiple human solid tumours: association with aberrant promoter methylation in renal cell carcinoma [J].
Dahl, E. ;
Wiesmann, F. ;
Woenckhaus, M. ;
Stoehr, R. ;
Wild, P. J. ;
Veeck, J. ;
Knuechell, R. ;
Klopocki, E. ;
Sauter, G. ;
Simon, R. ;
Wieland, W. F. ;
Walter, B. ;
Denzinger, S. ;
Hartmann, A. ;
Hammerschmied, C. G. .
ONCOGENE, 2007, 26 (38) :5680-5691
[9]   Targeting Wnt Signaling in Colon Cancer Stem Cells [J].
de Sousa, E. Melo Felipe ;
Vermeulen, Louis ;
Richel, Dick ;
Medema, Jan Paul .
CLINICAL CANCER RESEARCH, 2011, 17 (04) :647-653
[10]   Epigenetic fingerprint in endometrial carcinogenesis The hypothesis of a uterine field cancerization [J].
Di Domenico, Marina ;
Santoro, Angela ;
Ricciardi, Carmela ;
Iaccarino, Mirella ;
Iaccarino, Stefania ;
Freda, Mariagrazia ;
Feola, Antonia ;
Sanguedolce, Francesca ;
Losito, Simona ;
Pasquali, Daniela ;
Sardo, Attilio Di Spiezio ;
Bifulco, Giuseppe ;
Nappi, Carmine ;
Bufo, Pantaleo ;
Guida, Maurizio ;
De Rosa, Gaetano ;
Abbruzzese, Alberto ;
Caraglia, Michele ;
Pannone, Giuseppe .
CANCER BIOLOGY & THERAPY, 2011, 12 (05) :447-457