Chemoaffinity capture of pre-targeted prostate cancer cells with magnetic beads.
Chemoaffinity capture of pre-targeted prostate cancer cells with magnetic beads.
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DOI：
10.1002/pros.22508
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发表时间：
2012-10-01
期刊：
影响因子：
2.8
通讯作者：
Berkman, Clifford E.
中科院分区：
文献类型：
--
作者：
Wu, Lisa Y.;Liu, Tiancheng;Hopkins, Mark R.;Davis, William C.;Berkman, Clifford E.
关键词：
循环中的前列腺循环肿瘤细胞（PCTC）从原发性肿瘤或转移瘤脱落，这直接导致大多数前列腺癌死亡。定量脱落的PCTC可以作为前列腺癌临床管理的指标，分离和去除PCTC可以潜在地减少前列腺癌转移，培养和表征捕获的PCTC可以促进个性化治疗方案的开发。前列腺特异性膜抗原（PSMA）是前列腺癌的既定生物标志物，其在与高级别原发性、雄激素非依赖性和转移性肿瘤相关的前列腺肿瘤细胞上强烈表达。用不可逆PSMA抑制剂生物素-PEG 12-CTT-54预靶向PSMA+（LNCaP）细胞的悬浮液，以用作诱饵，从而使用链霉亲和素包被的磁珠捕获PSMA+细胞。将减少数量的LNCaP细胞掺入血液中以确定细胞捕获效率、回收率和活力。在使用LNCaP细胞和WBC的混合物以及掺有LNCaP细胞的血液样品的两个模型实验中，实现了捕获PSMA+细胞的高选择性、回收率和活力。从1 mL血液中捕获低至10个细胞，存活率接近90%。更重要的是，捕获的细胞随后可以在体外繁殖。这种方法的检测，分离和培养的PCTC从外周血中可以作为一个有效的工具，用于检测转移性前列腺癌，治疗监测，和个性化治疗的发展的基础上的PCTC化疗策略的反应。
Prostate circulating tumor cells (PCTCs) in circulation are shed from either a primary tumor or metastases, which are directly responsible for most prostate cancer deaths. Quantifying exfoliated PCTCs may serve as an indicator for the clinical management of prostate cancer, isolating and removing of PCTCs could potentially reduce prostate cancer metastasis, and culturing and characterizing captured PCTCs could facilitate the development of personalized treatment options. Prostate-specific membrane antigen (PSMA) is an established biomarker for prostate cancer being strongly expressed on prostate tumor cells associated with high-grade primary, androgen independent, and metastatic tumors. Suspensions of PSMA+ (LNCaP) cells were pre-targeted with the irreversible PSMA inhibitor biotin-PEG12-CTT-54 to serve as a bait to capture PSMA+ cells using streptavidin-coated magnetic beads. Decreasing numbers of LNCaP cells were spiked into blood to determine the cell captured efficiency, recovery and viability. High selectivity, recovery, and viability were achieved for the capture of PSMA+ cells in both model experiments with mixtures of LNCaP cells and WBCs as well as blood samples spiked with LNCaP cells. As low as 10 cells were captured from 1 mL of blood with nearly 90% viability. More importantly, captured cells could be subsequently propagated in vitro. This methodology for the detection, isolation, and culture of PCTCs from peripheral blood can serve as an effective tool for the detection of metastatic prostate cancer, treatment monitoring, and the development of personalized therapy based on the responsiveness of PCTCs to chemotherapeutic strategies.
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