Prostate Stem Cell Antigen: A Jekyll and Hyde Molecule?

• Published in: Clinical cancer research Vol. 16; no. 14; pp. 3533 - 3538
• Main Authors: SAEKI, Norihisa, JIAN GU, YOSHIDA, Teruhiko, XIFENG WU
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 15.07.2010
• Subjects: Antigens, Neoplasm - genetics; Antigens, Neoplasm - immunology; Antigens, Neoplasm - metabolism; Antineoplastic agents; Biological and medical sciences; Biomarkers, Tumor - genetics; Biomarkers, Tumor - immunology; Biomarkers, Tumor - metabolism; Female; GPI-Linked Proteins - genetics; GPI-Linked Proteins - immunology; GPI-Linked Proteins - metabolism; Humans; Male; Medical sciences; Models, Biological; Neoplasm Proteins - genetics; Neoplasm Proteins - immunology; Neoplasm Proteins - metabolism; Pancreatic Neoplasms - diagnosis; Pancreatic Neoplasms - genetics; Pancreatic Neoplasms - metabolism; Pharmacology. Drug treatments; Prostatic Neoplasms - diagnosis; Prostatic Neoplasms - genetics; Prostatic Neoplasms - metabolism; Urinary Bladder Neoplasms - diagnosis; Urinary Bladder Neoplasms - genetics; Urinary Bladder Neoplasms - metabolism; Prostate stem cell antigen; Molecules; Tumoral marker
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.ccr-09-3169

Prostate stem cell antigen (PSCA) is a glycosylphosphatidylinositol (GPI)-anchored cell surface protein. Although PSCA is thought to be involved in intracellular signaling, much remains unknown about its physiological function and regulatory mechanism in normal and cancer cells. It is up-regulated in several major cancers including prostate, bladder, and pancreatic cancers. The expression of PSCA is positively correlated with advanced clinical stage and metastasis in prostate cancers and is also associated with malignant progression of premalignant prostate lesions. Therefore, PSCA has been proposed as a biomarker of diagnosis and prognosis, as well as a target of therapy for these cancers. In addition, PSCA has also shown clinical potential in immunotherapy as a prostate-specific antigen, which, when presented by dendritic cells, may elicit strong tumor-specific immunity. In contrast, PSCA is down-regulated in esophageal and gastric cancer and may have a tumor-suppressing function in the gastric epithelium. Recent exciting findings that genetic variations of PSCA conferred increased risks of gastric cancer and bladder cancer have opened up a new avenue of research about the pathological function of PSCA. PSCA seems to be a Jekyll and Hyde molecule that plays differential roles, tumor promoting or suppressing, depending on the cellular context.