Real-Time Monitoring of Rare Circulating Hepatocellular Carcinoma Cells in an Orthotopic Model by In Vivo Flow Cytometry Assesses Resection on Metastasis
Real-Time Monitoring of Rare Circulating Hepatocellular Carcinoma Cells in an Orthotopic Model by In Vivo Flow Cytometry Assesses Resection on Metastasis
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DOI：
10.1158/0008-5472.can-11-3733
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发表时间：
2012-05-15
期刊：
影响因子：
11.2
通讯作者：
Wei, Xun-Bin
中科院分区：
文献类型：
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作者：
Fan, Zhi-Chao;Yan, Jun;Wei, Xun-Bin
循环肿瘤细胞（CTC）的命运是转移和复发的重要决定因素，导致肝细胞癌（HCC）的大多数死亡。因此，ctc的量化被证明是诊断、分层和监测转移性疾病患者的新兴工具。体内流式细胞术能够连续、无创地监测荧光标记的ctc的动态。在这里，我们结合体内流式细胞术技术和gfp转染的HCC原位转移瘤模型来监测CTC动态。我们的体内流式细胞术比传统流式细胞术的全血分析灵敏度高约1.8倍。我们发现原位和皮下肿瘤模型的CTC动力学有显著差异。我们还研究了肝切除术是否促进或限制晚期HCC的血行转移。我们的研究结果表明，CTCs和早期转移的数量在切除后显著减少。切除明显限制了血液转移和远处转移。在我们的原位肿瘤模型中，CTC动力学与肿瘤生长有关。远处转移灶的数量和大小与CTC动态相对应。新的体内流式细胞术技术结合原位肿瘤模型，可能为肿瘤血行转移提供新的认识和指导癌症治疗。癌症Res;72 (10);2683 - 91。(c) 2012年aacr。
The fate of circulating tumor cells (CTC) is an important determinant of metastasis and recurrence, which leads to most deaths in hepatocellular carcinoma (HCC). Therefore, quantification of CTCs proves to be an emerging tool for diagnosing, stratifying, and monitoring patients with metastatic diseases. In vivo flow cytometry has the capability to monitor the dynamics of fluorescently labeled CTCs continuously and noninvasively. Here, we combine in vivo flow cytometry technique and a GFP-transfected HCC orthotopic metastatic tumor model to monitor CTC dynamics. Our in vivo flow cytometry has approximately 1.8-fold higher sensitivity than whole blood analysis by conventional flow cytometry. We found a significant difference in CTC dynamics between orthotopic and subcutaneous tumor models. We also investigated whether liver resection promotes or restricts hematogenous metastasis in advanced HCC. Our results show that the number of CTCs and early metastases decreases significantly after the resection. The resection prominently restricts hematogenous metastasis and distant metastases. CTC dynamics is correlated with tumor growth in our orthotopic tumor model. The number and size of distant metastases correspond to CTC dynamics. The novel in vivo flow cytometry technique combined with orthotopic tumor models might provide insights to tumor hematogenous metastasis and guidance to cancer therapy. Cancer Res; 72(10); 2683-91. (C) 2012 AACR.