EMT circulating tumor cells detected by cell-surface vimentin are associated with prostate cancer progression.

EMT circulating tumor cells detected by cell-surface vimentin are associated with prostate cancer progression.
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细胞表面波形蛋白检测到的 EMT 循环肿瘤细胞与前列腺癌进展相关

DOI:
10.18632/oncotarget.17632
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发表时间:
2017-07-25
期刊:
影响因子:
--
通讯作者:
Li S
Li S
中科院分区:
其他
文献类型:
--
作者:
Satelli A;Batth I;Brownlee Z;Mitra A;Zhou S;Noh H;Rojas CR;Li H;Meng QH;Li S

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循环肿瘤细胞(CTC)领域的最新进展已显示出这种基于液体活检的患者预后的前景。然而,并非所有的循环细胞都是肿瘤细胞,如缺乏肿瘤特异性标志物所证明的。目前用于捕获CTC(CellSearch)的FDA标准依赖于上皮标记物,并且通过CellSearch捕获的细胞不能被认为已经经历EMT。因此,很难确定任何间充质或EMT样CTC的存在和相关性。为了解决这一技术差距,我们最近发现了细胞表面波形蛋白(CSV)作为检测肉瘤,乳腺癌和结肠癌间充质CTC的标志物的实用性。在这里,我们研究了48例前列腺癌(PCA)患者的外周血样本,包括激素敏感和去势抵抗亚组。分析血液样品的三种不同性质,包括我们自己的基于CSV的CTC计数(使用针对CSV的84-1 mAb)、基于CellSearch的上皮CTC计数和血清前列腺特异性抗原(PSA)定量。我们的数据表明,与CellSearch相比,基于CSV的方法具有更高的灵敏度和特异性。此外,我们在去势抵抗患者中观察到显著更大数量的CTC,如通过我们的CSV方法而不是CellSearch测量的。我们的数据表明,CSV引导的CTC计数可能具有预后价值,应进一步验证作为一种可能的测量PCA进展到致命的,雄激素非依赖性的形式。
Recent advances in the field of circulating tumor cells (CTC) have shown promise in this liquid biopsy-based prognosis of patient outcome. However, not all of the circulating cells are tumor cells, as evidenced by a lack of tumor-specific markers. The current FDA standard for capturing CTCs (CellSearch) relies on an epithelial marker and cells captured via CellSearch cannot be considered to have undergone EMT. Therefore, it is difficult to ascertain the presence and relevance of any mesenchymal or EMT-like CTCs. To address this gap in technology, we recently discovered the utility of cell-surface vimentin (CSV) as a marker for detecting mesenchymal CTCs from sarcoma, breast, and colon cancer. Here we studied peripheral blood samples of 48 prostate cancer (PCA) patients including hormone sensitive and castration resistant sub-groups. Blood samples were analyzed for three different properties including our own CSV-based CTC enumeration (using 84-1 mAb against CSV), CellSearch-based epithelial CTC counts, and serum prostate-specific antigen (PSA) quantification. Our data demonstrated that in comparison with CellSearch, the CSV-based method had greater sensitivity and specificity. Further, we observed significantly greater numbers of CTCs in castration resistant patients as measured by our CSV method but not CellSearch. Our data suggests CSV-guided CTC enumeration may hold prognostic value and should be further validated as a possible measurement of PCA progression towards the deadly, androgen-independent form.
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