PMID- 34294841
OWN - NLM
STAT- MEDLINE
DCOM- 20211109
LR  - 20211109
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 11
IP  - 1
DP  - 2021 Jul 22
TI  - Diagnostic potential of serum extracellular vesicles expressing prostate-specific 
      membrane antigen in urologic malignancies.
PG  - 15000
LID - 10.1038/s41598-021-94603-9 [doi]
LID - 15000
AB  - 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-naive 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.
CI  - (c) 2021. The Author(s).
FAU - Kawakami, Kyojiro
AU  - Kawakami K
AD  - Research Team for Mechanism of Aging, Tokyo Metropolitan Institute of 
      Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan.
FAU - Fujita, Yasunori
AU  - Fujita Y
AD  - Biological Process of Aging, Tokyo Metropolitan Institute of Gerontology, 35-2 
      Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan.
FAU - Kato, Taku
AU  - Kato T
AD  - Department of Urology, Asahi University Hospital, 3-23 Hashimotocho, Gifu, Gifu, 
      500-8523, Japan.
FAU - Horie, Kengo
AU  - Horie K
AD  - Department of Urology, Gifu University Graduate School of Medicine, 1-1 Yanagido, 
      Gifu, Gifu, 501-1193, Japan.
FAU - Koie, Takuya
AU  - Koie T
AD  - Department of Urology, Gifu University Graduate School of Medicine, 1-1 Yanagido, 
      Gifu, Gifu, 501-1193, Japan.
FAU - Umezawa, Keitaro
AU  - Umezawa K
AD  - Research Team for Mechanism of Aging, Tokyo Metropolitan Institute of 
      Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan.
FAU - Tsumoto, Hiroki
AU  - Tsumoto H
AD  - Research Team for Mechanism of Aging, Tokyo Metropolitan Institute of 
      Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan.
FAU - Miura, Yuri
AU  - Miura Y
AD  - Research Team for Mechanism of Aging, Tokyo Metropolitan Institute of 
      Gerontology, 35-2 Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan.
FAU - Katagiri, Yasuo
AU  - Katagiri Y
AD  - Department of Pathology, Gifu University Hospital, 1-1 Yanagido, Gifu, Gifu, 
      501-1193, Japan.
FAU - Miyazaki, Tatsuhiko
AU  - Miyazaki T
AD  - Department of Pathology, Gifu University Hospital, 1-1 Yanagido, Gifu, Gifu, 
      501-1193, Japan.
FAU - Ohsawa, Ikuroh
AU  - Ohsawa I
AD  - Biological Process of Aging, Tokyo Metropolitan Institute of Gerontology, 35-2 
      Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan.
FAU - Mizutani, Kosuke
AU  - Mizutani K
AD  - Department of Urology, Gifu University Graduate School of Medicine, 1-1 Yanagido, 
      Gifu, Gifu, 501-1193, Japan. mizutech@gifu-u.ac.jp.
FAU - Ito, Masafumi
AU  - Ito M
AD  - Biological Process of Aging, Tokyo Metropolitan Institute of Gerontology, 35-2 
      Sakae-cho, Itabashi-ku, Tokyo, 173-0015, Japan. mito@tmig.or.jp.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210722
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Membrane Proteins)
RN  - 0 (TIMD4 protein, human)
RN  - EC 3.4.21.77 (Prostate-Specific Antigen)
SB  - IM
MH  - Animals
MH  - Carcinoma, Renal Cell/*diagnosis/metabolism/pathology
MH  - Cell Line, Tumor
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Extracellular Vesicles/*metabolism
MH  - Humans
MH  - Kidney Neoplasms/*diagnosis/metabolism/pathology
MH  - Male
MH  - Membrane Proteins/*metabolism
MH  - Mice
MH  - Neoplasm Transplantation
MH  - Prostate-Specific Antigen/*metabolism
MH  - Prostatic Neoplasms/*diagnosis/metabolism/pathology
MH  - Sensitivity and Specificity
PMC - PMC8298409
COIS- M.I. reports a grant from The Grant-in-Aid from The Ministry of Education, 
      Culture, Sports, Science, and Technology of Japan. Gifu University (K.M.), Tokyo 
      Metropolitan Institute of Gerontology (K.K., Y.F., and M.I.) and FUJIFILM Wako 
      Pure Chemical Corporation (Osaka, Japan) have filed patent application related to 
      this research. The other authors declare no conflicts of interest associated with 
      this manuscript.
EDAT- 2021/07/24 06:00
MHDA- 2021/11/10 06:00
PMCR- 2021/07/22
CRDT- 2021/07/23 06:31
PHST- 2021/02/06 00:00 [received]
PHST- 2021/07/09 00:00 [accepted]
PHST- 2021/07/23 06:31 [entrez]
PHST- 2021/07/24 06:00 [pubmed]
PHST- 2021/11/10 06:00 [medline]
PHST- 2021/07/22 00:00 [pmc-release]
AID - 10.1038/s41598-021-94603-9 [pii]
AID - 94603 [pii]
AID - 10.1038/s41598-021-94603-9 [doi]
PST - epublish
SO  - Sci Rep. 2021 Jul 22;11(1):15000. doi: 10.1038/s41598-021-94603-9.