Royuela M, De Miguel M P, Bethencourt F R, Sanchez-Chapado M, Fraile B, Paniagua R
Department of Cell Biology and Genetics, University of Alcalá, Alcalá de Henares, Madrid, Spain.
Growth Factors. 1998;16(2):101-10. doi: 10.3109/08977199809002121.
An immunohistochemical and semiquantitative comparative study of transforming growth factor beta 1 (TGF-beta 1) and its receptor types I (TGF-beta RI) and II (TGF-beta RII) 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-beta 1 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 immunostained. Some stromal cells were also stained. Immunostaining to TGF-beta RI 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-beta RII 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 possess both receptor types, and hence can transduce TGF-beta 1 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-beta 1 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-beta 1 and possess both types of TGF-beta 1 receptors, and thus, both epithelial cell types are susceptible to TGF-beta 1 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-beta RIIs seem to be more numerous than TGF-beta RIs and this lead us to hypothesize that these incomplete receptors might be a protection against the inhibition caused by TGF-beta 1 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.
对转化生长因子β1（TGF-β1）及其I型受体（TGF-βRI）和II型受体（TGF-βRII）进行了免疫组织化学和半定量比较研究，研究对象包括正常前列腺组织、良性前列腺增生（BPH）患者的前列腺组织以及前列腺腺癌患者的前列腺组织。在正常前列腺组织中，对TGF-β1的免疫反应仅限于基底上皮细胞。结缔组织基质中的一些细胞也被染色。在BPH中，上皮的柱状（分泌）细胞也观察到免疫标记。在前列腺腺癌中，所有上皮细胞类型均呈强免疫染色。一些基质细胞也被染色。对TGF-βRI的免疫染色仅存在于正常前列腺组织的基底细胞中。在BPH中，这种免疫反应见于整个上皮以及一些基质细胞。在前列腺癌中，该受体的免疫染色模式与BPH相似，但上皮细胞中的染色更强。对TGF-βRII的免疫反应出现在正常前列腺上皮的一些基底细胞和一些散在的柱状细胞中。在BPH切片中，这种模式得以维持，并且在基质中也观察到微弱的免疫标记。在前列腺癌中，所有上皮细胞均呈强标记。在基质中，免疫标记与BPH标本相似。本研究结果表明，在正常前列腺组织中，仅上皮的基底细胞同时拥有两种受体类型，因此能够在细胞内转导TGF-β1信号。基底细胞也可以分泌这种生长因子，该因子对它们起到自分泌抑制生长因子的作用。此外，TGF-β1在某些区域由基质细胞分泌，然后作为这些区域基底细胞的旁分泌生长因子。在BPH中，除了基底细胞外，一些分泌性柱状细胞也分泌TGF-β1并拥有两种TGF-β1受体类型，因此，两种上皮细胞类型均易受TGF-β1作用的影响。由于两种受体类型也存在于一些基质细胞中，这些细胞除了向上皮细胞进行旁分泌外，还进行自分泌。TGF-βRII似乎比TGF-βRI数量更多，这使我们推测这些不完全受体可能是一种针对TGF-β1作用引起的抑制的保护机制。在前列腺癌中，所有细胞类型均表现出与BPH相同的特征，尽管两种受体类型数量相似，因此，上述保护机制不会发生。
