Alpha₂ macroglobulin, a PSA binding protein, is expressed in human prostate stroma

BACKGROUND. 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, α₂ macroglobulin (α₂-M) is one of the most interesting. α₂-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 α₂-M expression in the human prostate. METHODS. 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 α₂-M expression in the prostate. RESULTS. Real-time RT-PCR results revealed that a 3.2-fold increase in α₂-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 α₂-M expression is primarily localized to the stromal compartment. Cultured primary stroma cells maintained α₂-M expression, while prostate epithelial cells had a significantly lower level of α₂-M expression. Furthermore, stromal cells in culture produce and secrete α₂-M in the medium. CONCLUSIONS. We identified α₂-M expression in the human prostate. An increased α₂-M expression appears to be associated with BPH. Considering the unique features of its protein binding and targeting properties, α₂-M expressed in the prostate may play an important role in regulating benign and malignant prostatic growth.