BERKELEY, CA (UroToday.com) - Semenogelins I (SgI) and II (SgII) constitute the major structural proteins in human semen and are well known to contribute to sperm clotting in the presence of Zn2+. After ejaculation, semenogelins are degraded into smaller fragments by prostate-specific antigen, resulting in clotted gel liquefaction and release of the trapped spermatozoa. Eppin (epidermal protease inhibitor) is mainly expressed and secreted in the epididymis and testis. It has been identified in a protein complex containing SgI in seminal plasma and on the surface of spermatozoa, which inhibits sperm motility.
Physiological functions of semenogelins and eppin in male reproductive organs have been thoroughly studied. In contrast, the biological role of these seminal plasma proteins in malignancies, including prostate cancer, is poorly understood. We recently showed increased expression of SgI and SgII in prostate cancer tissues, compared with corresponding benign prostate (Prostate 71: 1108-1114, 2011). However, perhaps due to small sample size (n = 70) with a relatively short follow-up duration (mean: 29.2 months), prognostic significance of semenogelin expression was unlikely conclusive. In the previous study, SgI was also found to promote the proliferation of androgen receptor-positive prostate cancer cell lines. In addition, we separately showed that the levels of eppin expression were more elevated in the 70 prostate cancers than in non-neoplastic prostate glands (Eur Urol 59: 1071-1072, 2011).
In the current article, we aimed to validate our earlier results in a larger patient cohort (n = 291) with longer follow-up (mean: 47.5 months). This would be the first large study to simultaneously investigate the expression (nuclear, cytoplasmic, and intraluminal) of SgI, SgII, and eppin in benign prostate, prostatic intraepithelial neoplasia (PIN), and prostate cancer tissues.
Significant increases in the expression of nuclear SgI and cytoplasmic eppin, as well as a significant decrease in nuclear eppin expression, were observed in prostate cancer, compared to benign or PIN glands. Higher expression of nuclear SgII in PIN than in benign or cancerous prostate was also noted. Moreover, nuclear SgI expression was suggested to be a reliable biomarker for biochemical recurrence after radical prostatectomy. Intraluminal expression of SgI, SgII, and eppin were all dramatically reduced in carcinoma, compared to benign and PIN glands, suggesting that carcinoma cells do not generally secrete a large amount of these proteins. These results may indicate the involvement of semenogelins and eppin in the development and progression of prostate cancer. Further functional analyses of these seminal plasma proteins are necessary to determine their biological significance in prostate cancer.
Written by:
Hiroshi Miyamoto, MD, PhD as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.
Attending Surgical Pathologist at Strong Memorial Hospital
Director of Genitourinary Pathology Fellowship Program
Associate Professor of Pathology and Laboratory Medicine
University of Rochester School of Medicine and Dentistry
601 Elmwood Avenue, Box 626
Rochester, NY 14642
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