Prostate-specific antigen triggers transformation of seminal α2-macroglobulin (α2-M) and its binding to α2-macroglobulin receptor/low-density lipoprotein receptor-related protein (α2-M-R/LRP) on human spermatozoa

PSA‐alpha‐2‐macroglobulin complex is enzymatically active in the serum of patients with advanced prostate cancer and can degrade circulating peptide hormones

“…A2M plays an underappreciated, but critical role in cancer biology based on its ability to act as a signaling molecule, a carrier for growth factors and a modulator of protease activity. Conformationally altered A2M can activate or inhibit signal transduction pathways through binding to membrane receptors . A2M binding to A2M receptor/LRP activates G‐protein activated pathways .…”

Human Epididymis Protein-4 (HE-4): A Novel Cross-Class Protease Inhibitor

“…Protein C inhibitor (PCI), α-2 macroglobulin (A2M) and α1-anti chymotrypsin (ACT) are three main inhibitors of PSA reported in human seminal fluid. Concentrations of these inhibitors in seminal fluid are low compared to PSA [41]–[43] suggesting there must be other inhibitors, which serve as main inhibitors. HE-4 seems to be one such inhibitor.…”

Human Kallikrein 4: Quantitative Study in Tissues and Evidence for Its Secretion into Biological Fluids

“…Thus, detection of low amounts of hK4 protein in serum becomes more difficult with formation of this complex. In contrast to findings in serum, similar hK4 complexes were not observed in seminal plasma (data not shown), although ␣ 2 -macroglobulin is known to be present in this fluid (50 ). One explanation may be that the amount of ␣ 2 -macroglobulin varies widely, ranging from 1 to 1000 g/L in seminal plasma (51 ), and that this is only a fraction of the protein found in serum, where concentrations range from 1.5 to 5 g/L in healthy individuals (52 ).…”