PSMA-positive membranes secreted from prostate cancer cells have potency to transform vascular endothelial cells into an angiogenic state.
PSMA-positive membranes secreted from prostate cancer cells have potency to transform vascular endothelial cells into an angiogenic state.
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DOI：
10.1002/pros.24237
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发表时间：
2021-12
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影响因子：
--
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中科院分区：
文献类型：
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前列腺特异性膜抗原（PSMA）在低分化、转移性和去势抵抗性前列腺癌中高度表达。最近，68Ga‐PSMA正电子发射断层扫描/计算机断层扫描已成功发展成为前列腺癌的有效诊断工具。然而，PSMA在前列腺肿瘤中的病理生理功能尚不清楚。应用免疫组织化学方法检测PSMA蛋白在人前列腺肿瘤内皮细胞中的表达。2019年，爱媛大学的机器人手术从前列腺癌患者身上切除了前列腺癌组织。在体外，我们制备了条件培养基（CM），该培养基来源于PSMA阳性的人前列腺癌细胞系LNCaP，并在胶原I凝胶上培养。然后，我们检测了用CM培养的人脐血管内皮细胞（HUVECs）中PSMA的表达。我们使用模拟血管生成的管形成实验，通过LNCaP衍生的CM处理HUVECs来评估血管生成活性。33例前列腺癌患者中有4例（12.1%）观察到PSMA和内皮细胞标志物CD31的免疫组化，以及PSMA‐表达的肿瘤内皮细胞。我们还发现，含有PSMA阳性膜的LNCaP衍生CM的10,000g颗粒部分，如微泡，将HUVECs的“PSMA阴性”转化为“PSMA阳性”。此外，用LNCaP衍生的CM的10,000g颗粒部分处理HUVECs可显著促进管的形成，以PSMA依赖的方式模拟血管生成。我们的研究结果表明PSMA阳性的肿瘤内皮细胞在人前列腺肿瘤中存在，促进前列腺癌组织的血管生成。
Prostate‐specific membrane antigen (PSMA) is highly expressed in poorly differentiated, metastatic, and castration‐resistant prostate cancers. Recently, 68Ga‐PSMA positron emission tomography/computed tomography has been successfully developed as an effective diagnostic tool for prostate cancer. However, the pathophysiological functions of PSMA in prostate tumors remain unclear. We examined the protein expression of PSMA in tumor endothelial cells in human prostate tumors by immunohistochemistry. Prostate cancer tissues were resected by robotic surgery in 2019 at Ehime University from patients with prostate cancer. In vitro, we prepared conditioned medium (CM) derived from a PSMA‐positive human prostate cancer cell line, LNCaP, cultured on collagen I gels. We then examined PSMA expression in human umbilical vascular endothelial cells (HUVECs) cultured with the CM. We assessed angiogenic activities by treatment of HUVECs with LNCaP‐derived CM using a tube formation assay that mimics angiogenesis. Immunohistochemistry of PSMA and CD31, a marker of endothelial cells, and PSMA‐expressing tumor endothelial cells were observed in 4 of 33 prostate cancer patients (12.1%). We also found that the 10,000g pellet fraction of the LNCaP‐derived CM containing PSMA‐positive membranes, such as microvesicles transformed HUVECs “PSMA‐negative” into “PSMA‐positive.” Furthermore, treatment of HUVECs with the 10,000g pellet fraction of the LNCaP‐derived CM significantly promoted tube formation, mimicking angiogenesis in a PSMA‐dependent manner. Our findings revealed the existence of PSMA‐positive tumor endothelial cells in human prostate tumors, which enhances tumor angiogenesis in prostate cancer tissues.
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影响因子：
5.4
作者：
Szatanek R;Baran J;Siedlar M;Baj-Krzyworzeka M
通讯作者：
Baj-Krzyworzeka M
影响因子：
3.7
作者：
Schmidt LH;Heitkötter B;Schulze AB;Schliemann C;Steinestel K;Trautmann M;Marra A;Hillejan L;Mohr M;Evers G;Wardelmann E;Rahbar K;Görlich D;Lenz G;Berdel WE;Hartmann W;Wiewrodt R;Huss S
通讯作者：
Huss S
影响因子：
5.8
作者：
Nomura N;Pastorino S;Jiang P;Lambert G;Crawford JR;Gymnopoulos M;Piccioni D;Juarez T;Pingle SC;Makale M;Kesari S
通讯作者：
Kesari S
DOI：
10.1007/s00259-015-3078-6
发表时间：
2015-07-01
影响因子：
9.1
作者：
Ceci, Francesco;Uprimny, Christian;Virgolini, Irene J.
通讯作者：
Virgolini, Irene J.
影响因子：
4
作者：
Kasoha, Mariz;Unger, Clara;Juhasz-Boess, Ingolf
通讯作者：
Juhasz-Boess, Ingolf