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Prostate-specific membrane antigen is produced in tumor-associated neovasculature
S S Chang1, D S O'Keefe, D J Bacich
1Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Abstract:
Prostate-specific membrane antigen (PSMA), a type II transmembrane protein, was originally thought to be strictly expressed in prostatic tissue, but recent studies have demonstrated PSMA protein expression in nonprostatic tumor neovasculature as well. Using immunohistochemistry, reverse transcription-PCR assays, and in situ hybridization, we have demonstrated PSMA mRNA transcripts and protein expression in the endothelium of tumor-associated neovasculature of multiple nonprostatic solid malignancies. In addition, we found no PSMA mRNA or protein expression in the vascular endothelial cells of corresponding benign tissue examples. Our findings expand the possible therapeutic role of PSMA and establish it as a unique biomarker specifically produced and expressed by tumor-associated neovasculature but not produced or expressed by normal vessels.
Insights
Prostate-specific membrane antigen (PSMA) is found in nonprostatic tumor blood vessels, not normal ones. This discovery highlights PSMA as a unique biomarker for tumor neovasculature, expanding its therapeutic potential.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Prostate-specific membrane antigen (PSMA) was initially considered exclusive to prostate tissue.
- Emerging evidence suggests PSMA expression in the neovasculature of nonprostate tumors.
Purpose of the Study:
- To investigate PSMA mRNA and protein expression in tumor-associated neovasculature of various nonprostatic solid malignancies.
- To compare PSMA expression in tumor neovasculature versus normal vasculature.
Main Methods:
- Immunohistochemistry
- Reverse transcription-polymerase chain reaction (RT-PCR) assays
- In situ hybridization
Main Results:
- PSMA mRNA transcripts and protein were detected in the endothelium of tumor-associated neovasculature across multiple nonprostatic solid tumors.
- No PSMA mRNA or protein expression was observed in vascular endothelial cells of corresponding benign tissues.
- This indicates PSMA is specifically associated with tumor neovasculature.
Conclusions:
- PSMA is expressed by the tumor-associated neovasculature in various nonprostatic solid malignancies.
- PSMA is not expressed in the vasculature of normal, benign tissues.
- PSMA represents a unique biomarker for tumor neovasculature, with potential therapeutic implications.