Vishnoi Monika, Peddibhotla Sirisha, Yin Wei, T Scamardo Antonio, George Goldy C, Hong David S, Marchetti Dario
Biomarker Research Program Center, Houston Methodist Research Institute, Houston, TX.
Department of Pathology &Immunology, Baylor College of Medicine, Houston, TX.
Sci Rep. 2015 Dec 3;5:17533. doi: 10.1038/srep17533.
Uncovering CTCs phenotypes offer the promise to dissect their heterogeneity related to metastatic competence. CTC survival rates are highly variable and this can lead to many questions as yet unexplored properties of CTCs responsible for invasion and metastasis vs dormancy. We isolated CTC subsets from peripheral blood of patients diagnosed with or without breast cancer brain metastasis. CTC subsets were selected for EpCAM negativity but positivity for CD44(+)/CD24(-) stem cell signature; along with combinatorial expression of uPAR and int β1, two markers directly implicated in breast cancer dormancy mechanisms. CTC subsets were cultured in vitro generating 3D CTC tumorspheres which were interrogated for biomarker profiling and biological characteristics. We identified proliferative and invasive properties of 3D CTC tumorspheres distinctive upon uPAR/int β1 combinatorial expression. The molecular characterization of uPAR/int β1 CTC subsets may enhance abilities to prospectively identify patients who may be at high risk of developing BCBM.
揭示循环肿瘤细胞（CTC）的表型有望剖析其与转移能力相关的异质性。CTC的存活率高度可变，这可能引发许多关于负责侵袭和转移与休眠的CTC尚未探索特性的问题。我们从诊断为有或无乳腺癌脑转移的患者外周血中分离出CTC亚群。选择EpCAM阴性但CD44(+)/CD24(-)干细胞标志物阳性的CTC亚群；以及uPAR和整合素β1的组合表达，这两个标志物直接参与乳腺癌休眠机制。将CTC亚群进行体外培养，生成三维CTC肿瘤球，并对其进行生物标志物分析和生物学特性研究。我们发现三维CTC肿瘤球的增殖和侵袭特性在uPAR/整合素β1组合表达时具有独特性。uPAR/整合素β1 CTC亚群的分子特征可能会增强前瞻性识别可能有高风险发生乳腺癌脑转移患者的能力。
