In vivo flow cytometry visualizes the effects of tumor resection on metastasis by real-time monitoring of rare circulating cancer cells

摘要

Hepatocellular carcinoma (HCC) is one of the most common malignancies in the world, with approximately 1,000,000 cases reported every year. The fate of circulating tumor cells (CTCs) is an important determinant of metastasis and recurrence, which lead to most deaths in HCC. Therefore, quantification of CTCs proves to be an emerging tool for diagnosing, stratifying and monitoring patients with metastatic diseases. In vivo flow cytometry (IVFC) has the capability to monitor the dynamics of fluorescently labeled CTCs continuously and non-invasively. Here, we combine IVFC technique and a GFP-transfected HCC orthotopic metastatic tumor model to monitor CTC dynamics. Our IVFC has ～1.8-fold higher sensitivity than whole blood analysis by conventional flow cytometry. We find out a significant difference of CTC dynamics between orthotopic and subcutaneous (s.c.) tumor models. We also investigate whether liver resection promotes or restricts hematogenous metastasis in advanced HCC. Our result shows that the number of CTCs and early metastases decreases after the resection. 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 IVFC technique combined with orthotopic tumor models might provide insights to tumor hematogenous metastasis and guidance to cancer therapy.