Down regulation of TGF-beta receptors in Human colorectal Canter

许多结直肠癌包膜细胞对转化生长因子- β (tgf - β)的抗增殖作用具有抗性。tgf - β也作为癌细胞间充质细胞的旁分泌因子。本研究的目的是检测tgf - β及其受体在人类结直肠癌组织中的表达，并确定其与肿瘤生长的关系。以10例人结直肠癌腺瘤、21例结直肠癌晚期和10例正常结直肠粘膜为对照，原位杂交检测TGF-beta_1ⅰ型和ⅱ型受体mRNA，并进行TGF-beta_1免疫组化染色。tgf - β受体mrna主要在正常结肠上皮细胞和腺瘤中表达。然而，tgf - β受体的mrna在21例晚期癌症患者中的7例中表达微弱，如果有的话。此外，在所有结直肠癌中均检测到TGF-beta_1 mRNA和该蛋白的强烈信号。tgf - β受体mrna和tgf - β _1蛋白也分布在成纤维细胞和间质内皮细胞中。通过tgf - β受体的转录下调，人类结肠癌从tgf - β介导的生长抑制中逃脱，以及tgf - β对基质形成和血管生成的影响，表明tgf - β在完整宿主中结肠癌进展中的可能作用。

Many colorectal canoer cells are resistant to the anti-proliferative effects of transforming growth factor-beta (TGF-beta). TGF-beta also acts as paracrine factor from cancer cells on their mesenchymal cells. The aim of this study was to examine the expression of TGF-beta and its receptors in human colorectal cancer tissue and determined any relationship with cancer growth. In situ hybridization detection of TGF-beta_1 type I and type II receptor mRNA and immunohistochemical staining of TGF-beta_1 were performed using 10 human colorectal adenomas, 21 colorectal advanced cancers and 10 normal colorectal mucosas as control. TGF-beta receptor mRNAs were expressed mainly by normal colorectal epithelial cells and adenoma. However, mRNAs for TGF-beta receptors were only faintly, if at all, expressed in 7 of 21 human advanced cancers. In addition, intense signals of TGF-beta_1 mRNA and the protein were detected in all colorectal cancers. TGF-beta receptor mRNAs and TGF-beta_1 protein were also distributed in fibroblasts and endothelial cells in the interstitum. The escape of human colon cancer from TGF-beta-mediated growth inhibition by transcriptional down-regulation of TGF-beta receptors as well as the effects of TGF-beta on stroma formation and angiogenesis indicate a possible role for TGF-beta in the progression of colon cancer in an intact host.