Valcz Gábor, Patai Arpád V, Kalmár Alexandra, Péterfia Bálint, Fűri István, Wichmann Barnabás, Műzes Györgyi, Sipos Ferenc, Krenács Tibor, Mihály Emese, Spisák Sándor, Molnár Béla, Tulassay Zsolt
Molecular Medicine Research Unit, Hungarian Academy of Sciences, Budapest, Hungary.
2nd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.
PLoS One. 2014 Nov 18;9(11):e106143. doi: 10.1371/journal.pone.0106143. eCollection 2014.
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.
基质-上皮相互作用的表观遗传变化在调节结直肠癌（CRC）细胞以及正常相邻肿瘤（NAT）区域形态正常但基因和表观遗传发生改变的上皮细胞方面至关重要。在此，我们证明了著名的Wnt抑制剂分泌型卷曲相关蛋白1（SFRP1）在基质肌成纤维细胞中保留蛋白表达，且从NAT组织到肿瘤，上皮表达逐渐降低。在这些区域，激光显微切割的肌成纤维细胞中的SFRP1未发生甲基化，而上皮细胞中部分发生高甲基化。相比之下，我们发现CRC基质中肌成纤维细胞来源的SFRP1发生了表观遗传沉默。我们的结果表明，肌成纤维细胞来源的SFRP1蛋白可能是NAT区域上皮增殖的旁分泌抑制剂，该信号的缺失可能会促进CRC中的肿瘤增殖。
