Center for Molecular Medicine, Maine Medical Center Research Institute, Scarborough, Maine, United States of America.
PLoS One. 2014 Jun 19;9(6):e100449. doi: 10.1371/journal.pone.0100449. eCollection 2014.
An increasing number of studies report that Cthrc1 is expressed in various cancer cells. The present study sought to identify which cells in tumors and remodeling tissues express Cthrc1 and investigate the range of circulating human Cthrc1 levels in health and disease.
METHODOLOGY/PRINCIPLE FINDINGS: Highly specific monoclonal antibodies were generated to detect Cthrc1 by ELISA in plasma and in tissues by immunohistochemistry. In human colon, gastric, breast, endometrial, pancreatic, kidney, lung and skin cancer, Cthrc1 was expressed by activated stromal cells and not the cancer cells themselves. Similarly, conditions evoking tissue remodeling, such as wound repair or angiotensin II-mediated hypertension, induced Cthrc1 expression in interstitial and adventitial fibroblasts and perivascular stromal cells. Levels of Cthrc1 in plasma from healthy subjects were near the lower detection limit except for individuals with red hair, who had up to several hundred fold higher levels. Elevated Cthrc1 was also found in patients with diabetes, inflammatory conditions, and infections, but not solid tumors. Transgenic mouse studies suggested that Cthrc1 expression by stromal cells does not contribute to circulating levels. In human pituitaries, Cthrc1 was expressed in the anterior and intermediate lobes with unencapsulated Cthrc1 accumulations typically surrounded by chromophobe cells.
We identify Cthrc1 as a marker for activated stromal cells. Cthrc1 is a pituitary hormone with significantly elevated levels in subjects carrying variant alleles of the melanocortin-1 receptor as wells as in patients with inflammatory conditions.
越来越多的研究报告表明 Cthrc1 在各种癌细胞中表达。本研究旨在确定肿瘤和重塑组织中的哪些细胞表达 Cthrc1，并研究健康和疾病人群中循环人 Cthrc1 水平的范围。
方法/原理发现：通过 ELISA 检测血浆中的 Cthrc1 和免疫组织化学检测组织中的 Cthrc1，生成了高度特异性的单克隆抗体。在人类结肠癌、胃癌、乳腺癌、子宫内膜癌、胰腺癌、肾癌、肺癌和皮肤癌中，Cthrc1 由激活的基质细胞表达，而不是癌细胞本身。同样，引起组织重塑的条件，如伤口修复或血管紧张素 II 介导的高血压，会诱导间质和外膜成纤维细胞和血管周围基质细胞表达 Cthrc1。除了红头发的个体外，健康受试者血浆中的 Cthrc1 水平接近检测下限，而红头发个体的水平高达数百倍。糖尿病、炎症和感染患者的 Cthrc1 水平也升高，但实体瘤患者没有。转基因小鼠研究表明，基质细胞表达的 Cthrc1 不会导致循环水平升高。在人类垂体中，Cthrc1 在垂体前叶和中叶表达，无包膜的 Cthrc1 堆积通常被嫌色细胞包围。
我们将 Cthrc1 鉴定为激活的基质细胞的标志物。Cthrc1 是一种垂体激素，携带黑素皮质素 1 受体变异等位基因的个体以及患有炎症性疾病的个体其水平显著升高。
