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. © 2004 Wiley‐Liss, Inc.