Transforming Growth Factor β and its Receptor Types I and II. Comparison in Human Normal Prostate, Benign Prostatic Hyperplasia, and Prostatic Carcinoma

Abstract

An immunohistochemical and semiquantitative comparative study of transforming growth factor β (TGF-β) and its receptor types I (TGF-βRI) and II (TGF-βRII) was carried out in normal prostates and in the prostates from men with benign prostatic hyperplasia (BPH), and men with prostatic adenocarcinoma. Immunoreaction to TGF-β1 was limited to the basal epithelial cells in the normal prostates. Some cells in the connective tissue stroma were also stained. In BPH immunolabelling was also observed in columnar (secretory) cells of the epithelium. In prostatic adenocarcinoma, all epithelial cell types were intensely immuno-stained. Some stromal cells were also stained. Immunostaining to TGF-βRI was only present in the basal cells in normal prostates. In BPH, this immunoreaction was found in the whole epithelium and in some stromal cells. In prostatic cancer, the immunostaining pattern for this receptor was similar to that of BPH but more intense in the epithelial cells. Immunoreactivity to TGF-βRII appeared in some basal cells and some scattered columnar cells of the normal prostate epithelium. In the BPH sections, this pattern was maintained, and a weak immunolabelling was also observed in the stroma. In prostate cancer, all epithelial cells appeared intensely labelled. In the stroma, immunolabelling was similar to that of the BPH specimens. The results of the present study suggest that, in normal prostates, only the basal cells of the epithelium posses both receptor types, and hence can transduce TGF-β1 signal intracellularly. The basal cells can also secrete this growth factor which would act as an autocrine inhibitory growth factor for them. In addition, TGF-β1 is secreted in some zones by stromal cells, acting then as a paracrine growth factor for basal cells in those areas. In BPH, in addition to the basal cells, some secretory columnar cells also secrete TGF-β1 and possess both types of TGF-β1 receptors, and thus, both epithelial cell types are susceptible to TGF-β1 action. Since both receptor types are also present in some stromal cells, these cells also perform an autocrine secretion, in addition to their paracrine secretion to the epithelial cells. TGF-βRIIs seem to be more numerous than TGF-βRIs and this lead us to hypothesize that these incomplete receptors might be a protection against the inhibition caused by TGF-β1 action. In prostatic carcinoma all cell types display the same characteristics as in BPH, although both receptor types are found in similar numbers, and thus, the above mentioned protection would not occur.