Abstract
Circulating tumor cells (CTCs) are putative markers of tumor prognosis and may serve to evaluate patient’s response to chemotherapy. CTCs are often detected as single cells but infrequently as clusters and are indicative of worse prognosis. In this study, we developed a short-term culture of nucleated blood cells which was applied to blood samples from breast, lung, esophageal and bladder cancer patients. Clusters of different degrees of compactness, classified as very tight, tight and loose were observed across various cancer types. These clusters show variable expression of cytokeratins. Cluster formation from blood samples obtained during the course of chemotherapy was found to be associated with disease progression and shorter overall survival. The short-term cultures offer a robust and highly reliable method for early prediction of treatment response in different cancer types.
Highlights
Microenvironment through the recruitment of granulocytes in Circulating tumor cells (CTCs) microemboli[17]
Another study reported the presence of giant macrophages associated with CTC possibly promoting their dissemination and survival in the circulation, together supporting the significance of the microenvironment in tumor growth, progression and metastasis[18]
We have further developed a robust method to quantify the CTC cluster formed across cancer types and during various treatment regimens
Summary
Microenvironment through the recruitment of granulocytes in CTC microemboli[17]. Another study reported the presence of giant macrophages associated with CTC possibly promoting their dissemination and survival in the circulation, together supporting the significance of the microenvironment in tumor growth, progression and metastasis[18]. We observed that in short-term cultures CTCs could form clusters comprising other cell types including macrophages and natural killer-like cells[19]. We recently established a short-term culture method using laser-ablated microwells that permits the expansion of CTCs from whole blood of breast cancer patients[19]. CTCs that were able to survive in short-term culture were shown to form multilayered cell clusters in association with NK cells and macrophages, possibly reflecting some association in vivo as described above. We have further developed a robust method to quantify the CTC cluster formed across cancer types and during various treatment regimens. These clusters were categorized into three cluster types based on the cell density. We utilized the cluster phenotype as a predictive indicator of treatment response and to determine the therapeutic efficacy of the drugs
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