Real-Time Monitoring of Rare Circulating Hepatocellular Carcinoma Cells in an Orthotopic Model byIn VivoFlow Cytometry Assesses Resection on Metastasis

Abstract

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. Ó2012 AACR.

Systemic Immune-Inflammation Index Predicts Prognosis of Patients after Curative Resection for Hepatocellular Carcinoma

“…As an integrated indicator based on peripheral lymphocyte, neutrophil, and platelets counts, the predictive value of the SII for tumor recurrence and metastasis might be elucidated by the function of the three kinds of cells, and the their close relationship with CTCs, which play an important role in the initiation of recurrence and metastases after surgery (29)(30)(31). The patients with an elevated preoperative SII usually have thrombocytopenia, neutrophilia, or lymphopenia, suggesting an elevated inflammatory status and weak immune response in patients.…”

Circulating Tumor Cells from Different Vascular Sites Exhibit Spatial Heterogeneity in Epithelial and Mesenchymal Composition and Distinct Clinical Significance in Hepatocellular Carcinoma

“…The results of prior animal studies have suggested that trafficking of tumor cells via bloodstream is involved in the induction of metastatic disease (2)(3)(4)(5)(6). However, the evidence derived from animal models differs significantly from human cancer.…”

Emerging techniques in molecular detection of circulating tumor cells

“…To enhance the sensitivity, a study combines in vivo flow cytometry technique and a green fluorescent protein-transfected hepatocellular carcinoma orthotopic metastatic tumor model to monitor CTC dynamics. With 1.8-fold higher sensitivity than conventional flow cytometry, this novel approach shows that CTC dynamics is correlated with tumor growth in the orthotopic tumor model while the number and size of distant metastases correspond to CTC dynamics [15].…”