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

Abstract

The quantification of circulating tumor cells (CTCs) is an emerging tool used to diagnose, stratify and monitor patients with metastatic diseases. In vivo flow cytometry (IVFC) has the capability to measure the dynamics of fluorescently labeled CTCs continuously and non-invasively. In this study, we monitored CTC dynamics in a GFP-transfected orthotopic tumor model of metastatic hepatocellular carcinoma (HCC) using IVFC. Our IVFC approach showed a 1.8-fold higher sensitivity than whole blood analysis by conventional flow cytometry and was able to distinguish CTC changes between orthotopic and subcutaneous tumor models. We also used our model to investigate whether liver resection promotes or restricts hematogenous metastasis in advanced HCC. Both the number of CTCs and early metastases decreased significantly after tumor resection. Resection also prominently restricted hematogenous and distant metastases. Importantly, CTC numbers correlated with tumor growth in the orthotopic tumor model, including the number and size of distant metastases. When combined with orthotopic tumor models, the novel IVFC technique presented here offers the capability to elucidate mechanisms that drive hematogenous metastasis and to monitor the efficacy of cancer therapy.