Prostatic acid phosphatase (PAP) (PAP)

Prostatic acid phosphatase (PAP), also known as Acid phosphatase 3 (ACP3), is a dimeric glycoprotein primarily produced by the glandular epithelium of the prostate (UniProt: P15309). It exists in two main isoforms: a secretory form that is a major component of seminal fluid and a transmembrane form involved in intracellular signaling. Historically, PAP was the first clinically significant serum biomarker for the diagnosis and monitoring of prostate cancer, though it has been largely replaced by prostate-specific antigen (PSA) in routine screening (PubMed: 23663744). Currently, PAP is the target of Sipuleucel-T, the first FDA-approved autologous cellular immunotherapy for metastatic castration-resistant prostate cancer, which works by priming the patient's immune system to recognize and attack PAP-expressing cells (FDA: Provenge Label). Beyond its role in the prostate, PAP functions as an ectonucleotidase in the spinal cord, where it dephosphorylates adenosine monophosphate (AMP) to adenosine. This activity is crucial for modulating pain, as the resulting adenosine activates A1 receptors to produce potent antinociceptive effects, making PAP a target of interest for chronic pain therapies (PubMed: 18842883, PubMed: 21807037).

Other names

Acid phosphatase 3ACPPACP3Prostatic acid phosphomonoesterase5'-nucleotidaseThiamine monophosphataseProstatic acid phosphatase 3

Sipuleucel-T is an autologous cellular immunotherapy that induces a T-cell mediated immune response against PAP-expressing cells by activating patient-derived antigen-presenting cells with a PAP-GM-CSF fusion protein (FDA: Provenge Label). Additionally, PAP acts as an ectonucleotidase that converts AMP to adenosine, which activates A1 receptors to suppress pain signaling (PubMed: 18842883).