Abstract
The prostate stem cell antigen (PSCA) is a glycosylphosphatidyl-inositol (GPI)-linked cell surface antigen expressed in normal prostate and overexpressed in the majority of prostate cancers and correlates with tumor grade and disease stage. Because PSCA has been described to be up-regulated in pancreatic cancer, the purpose was to evaluate the expression of PSCA in human pancreatic cancer. Furthermore, the therapeutic efficacy of a monoclonal anti-PSCA antibody in an in vivo pancreatic cancer model was determined. The expression of PSCA in human pancreatic cancer tissues was determined and compared with chronic pancreatitis and normal pancreas by quantitative reverse transcriptase-polymerase chain reaction. Therapeutic efficacy of the monoclonal anti-PSCA antibody 1G8 was examined in Capan-1 pancreatic tumors grown as subcutaneous grafts in athymic nude mice. PSCA was strongly up-regulated in human pancreatic cancer compared with chronic pancreatitis and normal pancreas. In addition, the PSCA protein was expressed on the cell surface of pancreatic cancer cells. Treatment with 1G8 significantly reduced tumor growth initiation in an in vivo pancreatic cancer xenograft model. In addition, antibody treatment of established tumors reduced tumor progression. These results show a potential therapeutic role for anti-PSCA antibodies in the treatment of pancreatic cancer. Furthermore, PSCA might serve as a novel marker in the diagnosis of pancreatic cancer.
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