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.
复制标题
DOI：
10.1038/s41598-021-94603-9
复制
发表时间：
2021-07-22
影响因子：
4.6
通讯作者：
Ito M
中科院分区：
文献类型：
--
作者：
Kawakami K;Fujita Y;Kato T;Horie K;Koie T;Umezawa K;Tsumoto H;Miura Y;Katagiri Y;Miyazaki T;Ohsawa I;Mizutani K;Ito M
我们的目的是开发一种夹心ELISA检测前列腺特异性膜抗原（PSMA）的小细胞外囊泡（EV）使用T细胞免疫球蛋白结构域和粘蛋白结构域的蛋白4（Tim 4）作为捕获分子的EV，并评估其在泌尿系统恶性肿瘤的诊断潜力。首先，我们优化了夹心ELISA测量由Tim 4从血清捕获的EV上的PSMA水平的条件，并发现使用从Tim 4释放的高度纯化的EV（其在血清中捕获EV）降低了背景。其次，我们通过研究小鼠前列腺癌（PC）移植模型证实了它的有效性。最后，我们测量了泌尿系恶性肿瘤患者血清中的PSMA-EV。转移性PC和去势抵抗性PC（CRPC）患者的PSMA-EV水平显著高于未经治疗的PC患者。在肾细胞癌（RCC）患者中，与无转移的患者相比，转移的患者中的PSMA-EV升高，这可能反映了肿瘤中PSMA阳性的新生血管的发展。总之，我们开发了一种夹心ELISA，用于使用通过Tim 4从血清中分离的高度纯化的EV检测PSMA-EV。我们的研究结果表明，PSMA-EVs可能是有用的诊断和监测不仅PC，但也RCC和可能其他富血管实体瘤。
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.
登录
查看更多内容
影响因子：
3.8
作者：
Kawakami K;Fujita Y;Matsuda Y;Arai T;Horie K;Kameyama K;Kato T;Masunaga K;Kasuya Y;Tanaka M;Mizutani K;Deguchi T;Ito M
通讯作者：
Ito M
影响因子：
16
作者：
Crescitelli R;Lässer C;Szabó TG;Kittel A;Eldh M;Dianzani I;Buzás EI;Lötvall J
通讯作者：
Lötvall J
影响因子：
4.4
作者：
Rosenberg-Hasson, Yael;Hansmann, Leo;Liedtke, Michaela;Herschmann, Iris;Maecker, Holden T.
通讯作者：
Maecker, Holden T.
影响因子：
2.8
作者：
Padda, Ranjit S.;Deng, Florence K.;Leong, Hon S.
通讯作者：
Leong, Hon S.
影响因子：
4.6
作者：
Park, Yong Hyun;Shin, Hyun Woo;Lee, Ji Youl
通讯作者：
Lee, Ji Youl