Multifocal epithelial tumors and field cancerization from loss of mesenchymal CSL signaling.
Multifocal epithelial tumors and field cancerization from loss of mesenchymal CSL signaling.
复制标题
DOI：
10.1016/j.cell.2012.03.048
复制
发表时间：
2012-06-08
期刊：
影响因子：
64.5
通讯作者：
Dotto GP
中科院分区：
文献类型：
--
作者：
Hu B;Castillo E;Harewood L;Ostano P;Reymond A;Dummer R;Raffoul W;Hoetzenecker W;Hofbauer GF;Dotto GP
目前尚不清楚多灶性上皮肿瘤周围的组织变化是癌症的原因还是结果。在这里，我们提供的证据表明，间充质Notch/CSL信号的缺失导致组织改变，包括基质萎缩和炎症，这是上皮肿瘤发生之前和潜在的触发因素。携带CSL/RBP-Jκ（一种关键的Notch效应因子）间质特异性缺失的小鼠，在皮肤萎缩和炎症后表现出自发的多灶性角化细胞肿瘤。csl缺失的真皮成纤维细胞通过上调c-Jun和c-Fos的表达，从而提高扩散生长因子、炎症细胞因子和基质重塑酶的水平，促进肿瘤细胞增殖。在人类皮肤样本中，皮肤鳞状细胞癌和多灶性癌前光化性角化病病变附近的间质场表现出Notch/CSL信号减少和相关的分子变化。重要的是，这些基因表达的变化也可由长波紫外线引起，而长波紫外线是一种已知的皮肤野区癌变和皮肤癌的环境原因。
It is currently unclear whether tissue changes surrounding multifocal epithelial tumors are a cause or consequence of cancer. Here, we provide evidence that loss of mesenchymal Notch/CSL signaling causes tissue alterations, including stromal atrophy and inflammation, which precede and are potent triggers for epithelial tumors. Mice carrying a mesenchymal-specific deletion of CSL/RBP-Jκ, a key Notch effector, exhibit spontaneous multifocal keratinocyte tumors that develop after dermal atrophy and inflammation. CSL-deficient dermal fibroblasts promote increased tumor cell proliferation through up-regulation of c-Jun and c-Fos expression and consequently higher levels of diffusible growth factors, inflammatory cytokines, and matrix remodeling enzymes. In human skin samples, stromal fields adjacent to cutaneous squamous cell carcinomas and multifocal premalignant actinic keratosis lesions exhibit decreased Notch/CSL signaling and associated molecular changes. Importantly, these changes in gene expression are also induced by UVA, a known environmental cause of cutaneous field cancerization and skin cancer.
登录
查看更多内容
影响因子：
21.3
作者：
Kolev, Vihren;Mandinova, Anna;Guinea-Viniegra, Juan;Hu, Bing;Lefort, Karine;Lambertini, Chiara;Neel, Victor;Dummer, Reinhard;Wagner, Erwin F.;Dotto, G. Paolo
通讯作者：
Dotto, G. Paolo
影响因子：
7.5
作者：
Watt FM;Estrach S;Ambler CA
通讯作者：
Ambler CA
影响因子：
50.3
作者：
O'Hagan HM;Wang W;Sen S;Destefano Shields C;Lee SS;Zhang YW;Clements EG;Cai Y;Van Neste L;Easwaran H;Casero RA;Sears CL;Baylin SB
通讯作者：
Baylin SB
影响因子：
8
作者：
Hinata, K;Gervin, AM;Khavari, PA
通讯作者：
Khavari, PA
影响因子：
10.5
作者：
Hu, Bing;Lefort, Karine;Dotto, G. Paolo
通讯作者：
Dotto, G. Paolo