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

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

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 m...

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Autores principales: 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
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2021
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Science
Q
Acceso en línea:https://doaj.org/article/648dd70978a8435eb6429fb1ecaa1541
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spelling oai:doaj.org-article:648dd70978a8435eb6429fb1ecaa15412021-12-02T17:03:50ZDiagnostic potential of serum extracellular vesicles expressing prostate-specific membrane antigen in urologic malignancies10.1038/s41598-021-94603-92045-2322https://doaj.org/article/648dd70978a8435eb6429fb1ecaa15412021-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-94603-9https://doaj.org/toc/2045-2322Abstract 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.Kyojiro KawakamiYasunori FujitaTaku KatoKengo HorieTakuya KoieKeitaro UmezawaHiroki TsumotoYuri MiuraYasuo KatagiriTatsuhiko MiyazakiIkuroh OhsawaKosuke MizutaniMasafumi ItoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
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
Diagnostic potential of serum extracellular vesicles expressing prostate-specific membrane antigen in urologic malignancies
description 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.
format article
author 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
author_facet 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
author_sort Kyojiro Kawakami
title Diagnostic potential of serum extracellular vesicles expressing prostate-specific membrane antigen in urologic malignancies
title_short Diagnostic potential of serum extracellular vesicles expressing prostate-specific membrane antigen in urologic malignancies
title_full Diagnostic potential of serum extracellular vesicles expressing prostate-specific membrane antigen in urologic malignancies
title_fullStr Diagnostic potential of serum extracellular vesicles expressing prostate-specific membrane antigen in urologic malignancies
title_full_unstemmed Diagnostic potential of serum extracellular vesicles expressing prostate-specific membrane antigen in urologic malignancies
title_sort diagnostic potential of serum extracellular vesicles expressing prostate-specific membrane antigen in urologic malignancies
publisher Nature Portfolio
publishDate 2021
url https://doaj.org/article/648dd70978a8435eb6429fb1ecaa1541
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