MSMB is one of the three major proteins secreted by the epithelial cells of the prostate and has a concentration in seminal plasma of 0.5 to 1 mg/mL Two comprehensive studies of beta-microseminoprotein in tissue have shown that it is secreted by epithelial cells in many other organs: liver, lung, breast, kidney, colon, stomach, pancreas, esophagus, duodenum, salivary glands, fallopian tube, corpus uteri, bulbourethral glands and cervix. This list corresponds closely to the sites from which all late onset cancers develop.
Evolution and structure
MSMB is a rapidly evolving protein. Solution structures of human and porcine MSMB show remarkable similarity despite having only 51% of amino acids in common. The C-terminus domain of MSMB contains two two-stranded β-sheets; these have no resemblance to other structural motifs. The rapid evolution of MSMB can be attributed to either sexual selection or innate pathogen defense; the wide distribution of MSMB in the body and the fungicidal properties of the C-terminus suggest that innate pathogen defense plays a role in driving this evolution.
Function
Beta-microseminoprotein is a member of the immunoglobulin binding factor family. This protein has been reported to have inhibin-like properties, though this finding has been disputed. It may have a role as an autocrine paracrine factor in uterine, breast and other female reproductive tissues. Two alternatively splicedtranscript variants encoding different isoforms are described for this gene. Despite having only 4 out of 11 amino acids in common, both the porcine and human fungicidal peptide on MSMB's C-terminus are potently fungicidal in the absence of calcium ions. The protein inhibits growth of cancer cells in an experimental model of prostate cancer, though this property is cell line specific.
Clinical significance
Two large genome-wide association studies showed that decreased expression of the MSMB protein caused by the rs10993994 single nucleotide polymorphism is associated with an increased risk of developing prostate cancer. A 2003 study proposed using a truncated form of the MSMB protein called PSP61 as a biomarker for benign prostatic hyperplasia : this study found PSP61 in the expressed prostatic secretion of 10 out of ten 10 men suffering from BPH, but did not find it in 10 out of 10 age-matched BPH-free men. This truncated form of the MSMB protein lacks the fungicidal peptide identified in 2012. The expression of MSMB is found to be decreased in prostate cancer, so it may be used as a biomarker for prostate cancer. Urinary MSMB has been found to be superior than urinary PSA at differentiating men with prostate cancer at all Gleason grades.
