Diagnostic potential of serum extracellular vesicles expressing prostate-specific membrane antigen in urologic malignancies

Kyojiro Kawakami, Yasunori Fujita, Taku Kato, Kengo Horie, Takuya Koie, Keitaro Umezawa, Hiroki Tsumoto, Yuri Miura, Yasuo Katagiri, Tatsuhiko Miyazaki, Ikuroh Ohsawa, Kosuke Mizutani, Masafumi Ito

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

We aimed to develop a sandwich ELISA to detect prostate-specific membrane antigen (PSMA) on small extracellular vesicles (EVs) using T-cell immunoglobulin domain and mucin domain-containing protein 4 (Tim4) as a capture molecule for EVs and to evaluate its diagnostic potential in urologic malignancies. First, we optimized the conditions for sandwich ELISA measuring the PSMA level on EVs captured from serum by Tim4 and found that the use of highly-purified EVs released from Tim4 that had captured EVs in serum reduced the background. Second, we confirmed its validity by studying mouse xenograft model for prostate cancer (PC). Lastly, we measured PSMA-EVs in serum of patients with urologic malignancies. The PSMA-EV levels were significantly higher in metastatic PC and castration-resistant PC (CRPC) patients than in therapy-naïve PC patients. In renal cell carcinoma (RCC) patients, PSMA-EVs were elevated in those with metastasis compared with those without metastasis, which may reflect the development of the neovasculature positive for PSMA in tumors. In conclusion, we developed a sandwich ELISA for detection of PSMA-EVs using highly-purified EVs isolated from serum by Tim4. Our results suggest that PSMA-EVs may be useful to diagnose and monitor not only PC but also RCC and possibly other hypervascular solid tumors.

Original languageEnglish
Article number15000
JournalScientific reports
Volume11
Issue number1
DOIs
Publication statusPublished - 12-2021
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • General

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