Prostate-Specific Membrane Antigen (PSMA) is a protein found on the surface of certain cells throughout the body. Its unique characteristics have drawn considerable attention in medical research. Scientists are investigating PSMA to understand its biological roles and implications in various health conditions, particularly for its potential in addressing specific diseases.
Understanding PSMA
PSMA is a protein encoded by the FOLH1 gene, which provides instructions for its production within cells. This protein is a type II transmembrane glycoprotein, spanning the cell membrane with a small portion inside and a larger part extending outside. PSMA exists as a dimer, formed by two identical protein units, and has a molecular weight of approximately 100 kDa due to modifications like glycosylation.
While its name includes “prostate-specific,” PSMA is not exclusively found in prostate cells. It is highly expressed on the surface of prostate cells, both normal and cancerous, but also appears in other tissues. These include parts of the small intestine, kidneys, and certain regions of the brain, though often at lower levels than in prostate cancer.
Biological Function of PSMA
The primary biological role of PSMA is its enzymatic activity as a glutamate carboxypeptidase II (GCPII). This enzyme cleaves glutamate from larger molecules. One of its functions involves folate metabolism, where it acts as a folate hydrolase.
In the intestine, PSMA breaks down polyglutamylated folates, producing monoglutamyl folates for absorption. PSMA also exhibits N-acetylated-alpha-linked-acidic dipeptidase (NAALADase) activity, particularly in the nervous system. Here, it hydrolyzes the neuropeptide N-acetylaspartylglutamate (NAAG) to release glutamate, influencing excitatory neurotransmission.
PSMA in Prostate Cancer Diagnosis
The overexpression of PSMA on prostate cancer cells makes it a valuable target for diagnostic imaging. PSMA PET (Positron Emission Tomography) scans leverage this to detect cancer cells throughout the body. A radioactive tracer, such as Gallium-68 (68Ga-PSMA-11), is injected and binds to PSMA-expressing cancer cells, allowing visualization.
This imaging technique can identify primary tumors, lymph node metastases, and distant spread, even at very low prostate-specific antigen (PSA) levels. PSMA PET scans offer advantages over traditional imaging methods like CT, MRI, and bone scans, detecting smaller tumors and providing more precise localization. This enhanced detection aids in more accurate staging and treatment planning for prostate cancer patients.
PSMA in Prostate Cancer Therapy
Beyond diagnosis, PSMA is also targeted for prostate cancer treatment through radionuclide therapy. This approach uses a radioactive isotope like Lutetium-177 (177Lu-PSMA-617) linked to a molecule that specifically binds to PSMA-expressing cancer cells. Once bound, the isotope delivers radiation directly to tumor cells, damaging their DNA and leading to cell death.
This method allows for precise radiation delivery while minimizing exposure to healthy tissues. Such therapies are primarily used for advanced metastatic castration-resistant prostate cancer (mCRPC) that has progressed despite other treatments. The theranostic approach, combining PSMA-targeted imaging with PSMA-targeted therapy, offers a personalized treatment strategy.
PSMA Beyond Prostate Cancer
While recognized for its role in prostate cancer, PSMA is also found in other tissues and conditions. It is expressed in the neovasculature, new blood vessels that supply tumors, across various other solid cancers. These include renal cell carcinoma, glioblastoma multiforme, thyroid cancer, and certain types of lung and breast cancer.
The presence of PSMA in these non-prostatic tumors suggests its potential for broader diagnostic and therapeutic applications. Researchers are exploring how PSMA-targeted agents might be used to image or treat these other malignancies.