Alpha(2) macroglobulin, a PSA binding protein, is expressed in human prostate stroma

Benign prostatic hyperplasia (BPH) is characterized as a stromal process. The stroma smooth muscle (SM) may alter its phenotype during the progression of BPH. We have identified gene transcripts that may be differentially expressed in BPH using a differential display method. Among the fragments isolated, alpha(2) macroglobulin (alpha(2)-M) is one of the most interesting. alpha(2)-M is a binding protein of a variety of proteinases, including prostatic specific antigen (PSA). It also plays roles in molecular trapping and targeting. In this study, we characterized alpha(2)-M expression in the human prostate. Differential display was used to identify and isolate the differentially expressed transcripts between normal prostate and BPH tissues. RT-PCR, Western blot, in situ hybridization, and immunohistochemistry were utilized to confirm and characterize alpha(2)-M expression in the prostate. Real-time RT-PCR results revealed that a 3.2-fold increase in alpha(2)-M mRNA expression is observed in BPH compared with normal prostate tissue. A 1.9-fold increase at protein level was also observed. In situ hybridization and immunohistochemistry showed that alpha(2)-M expression is primarily localized to the stromal compartment. Cultured primary stroma cells maintained alpha(2)-M expression, while prostate epithelial cells had a significantly lower level of alpha(2)-M expression. Furthermore, stromal cells in culture produce and secrete alpha(2)-M in the medium. We identified alpha(2)-M expression in the human prostate. An increased alpha(2)-M expression appears to be associated with BPH. Considering the unique features of its protein binding and targeting properties, alpha(2)-M expressed in the prostate may play an important role in regulating benign and malignant prostatic growth.