Down regulation of TGF-beta receptors in Human colorectal Canter

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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.