Prostate specific membrane antigen (PSMA) expression in primary gliomas and breast cancer brain metastases.
Prostate specific membrane antigen (PSMA) expression in primary gliomas and breast cancer brain metastases.
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DOI：
10.1186/1475-2867-14-26
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发表时间：
2014-03-20
影响因子：
5.8
通讯作者：
Kesari S
中科院分区：
文献类型：
--
作者：
Nomura N;Pastorino S;Jiang P;Lambert G;Crawford JR;Gymnopoulos M;Piccioni D;Juarez T;Pingle SC;Makale M;Kesari S
原发性和继发性脑癌具有高度的治疗抗性，其显著的血管生成作为潜在的治疗靶点引起了人们的兴趣。最近的观察表明，原发性高级别胶质瘤的微血管内皮表达前列腺特异性膜抗原（PSMA）。乳腺癌表达PSMA，它们经常形成继发性脑肿瘤。因此，我们在这里报告了我们的初步研究，通过检查所有胶质瘤等级（19例患者）和乳腺癌脑转移（5例患者）中的PSMA水平，探讨了PSMA靶向脑肿瘤和转移性乳腺肿瘤的可行性。从档案材料和尸检的正常脑组织中获得肿瘤标本。对组织进行染色并探测PSMA，并使用自动化硬件和软件对表达水平进行成像和定量。胶质瘤亚型、乳腺肿瘤和乳腺肿瘤脑转移瘤的PSMA染色强度与正常进行统计学比较。正常脑微血管（4例尸检）未对PSMA染色，而小部分（<5%）健康神经元染色，并被完整的血脑屏障包围。高血管生成的IV级胶质瘤的肿瘤微血管显示出强烈的PSMA染色，其在患者之间变化并且显著高于正常脑（p < 0.05）。I级胶质瘤显示中度血管染色，而II级和III级胶质瘤无血管染色，但少数（<2%）肿瘤细胞染色。原发性乳腺癌组织和相关的脑转移瘤均表现出血管PSMA染色，尽管转移性病变的染色强度通常较低。我们的研究结果与先前显示PSMA在神经胶质瘤和乳腺癌脑转移瘤血管中表达的数据一致，并扩展了这些数据。这些结果为更全面的研究提供了理论基础，以探索PSMA靶向药物来治疗具有表达PSMA的血管系统的继发性脑肿瘤。此外，考虑到PSMA参与血管生成、细胞信号传导、肿瘤存活和侵袭，表征其表达可能有助于指导以后对低度胶质瘤进展为胶质母细胞瘤的过程的了解甚少的研究。
Primary and secondary brain cancers are highly treatment resistant, and their marked angiogenesis attracts interest as a potential therapeutic target. Recent observations reveal that the microvascular endothelium of primary high-grade gliomas expresses prostate specific membrane antigen (PSMA). Breast cancers express PSMA and they frequently form secondary brain tumors. Hence we report here our pilot study addressing the feasibility of PSMA targeting in brain and metastatic breast tumors, by examining PSMA levels in all glioma grades (19 patients) and in breast cancer brain metastases (5 patients). Tumor specimens were acquired from archival material and normal brain tissues from autopsies. Tissue were stained and probed for PSMA, and the expression levels imaged and quantified using automated hardware and software. PSMA staining intensities of glioma subtypes, breast tumors, and breast tumor brain metastases were compared statistically versus normals. Normal brain microvessels (4 autopsies) did not stain for PSMA, while a small proportion (<5%) of healthy neurons stained, and were surrounded by an intact blood brain barrier. Tumor microvessels of the highly angiogenic grade IV gliomas showed intense PSMA staining which varied between patients and was significantly higher (p < 0.05) than normal brain. Grade I gliomas showed moderate vessel staining, while grade II and III gliomas had no vessel staining, but a few (<2%) of the tumor cells stained. Both primary breast cancer tissues and the associated brain metastases exhibited vascular PSMA staining, although the intensity of staining was generally less for the metastatic lesions. Our results align with and extend previous data showing PSMA expression in blood vessels of gliomas and breast cancer brain metastases. These results provide a rationale for more comprehensive studies to explore PSMA targeted agents for treating secondary brain tumors with PSMA expressing vasculature. Moreover, given that PSMA participates in angiogenesis, cell signaling, tumor survival, and invasion, characterizing its expression may help guide later investigations of the poorly understood process of low grade glioma progression to glioblastoma.
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影响因子：
4.9
作者：
Kularatne, Sumith A.;Wang, Kevin;Low, Philip S.
通讯作者：
Low, Philip S.
DOI：
10.1111/j.1742-4658.2009.07177.x
发表时间：
2009-09
期刊：
The FEBS journal
影响因子：
--
作者：
Kim WY;Lee HY
通讯作者：
Lee HY
影响因子：
11.5
作者：
Leenders, WPJ;Küsters, B;de Waal, R
通讯作者：
de Waal, R
影响因子：
3.3
作者：
Haffner, Michael C.;Kronberger, Irmgard E.;Bander, Neil H.
通讯作者：
Bander, Neil H.
影响因子：
10.5
作者：
Hambardzumyan, Dolores;Becher, Oren J.;Holland, Eric C.
通讯作者：
Holland, Eric C.