Retrieval of Disseminated Tumor Cells Colonizing the Bone in Murine Breast Cancer Metastasis Models
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In breast cancer, the most frequent site of metastasis is bone. Disseminated tumor cells (DTCs) can be detected in the bone marrow of patients by their expression of epithelial or oncogenic markers , and the presence and frequency of these DTCs are associated with poor prognosis. However, many of the details behind this process remain elusive, including the biological properties and fates of these apparently indolent cancer cells. To provide pre-clinical models of DTCs, we have developed a procedure that allows for controlled and enhanced delivery of tumor cells to the bone in animal experiments via injection into the iliac artery of the hind limb . To our surprise, we found that most cancer cells became integrated into the solid bone matrix shortly after arriving in the bone, and only a minority can be flushed out with the bone marrow. Here we describe a method that helps to retrieve DTCs homing to the bone in which we achieve an improved recovery of those tumor cells closely associated with the bone microenvironment. In our view it is especially important to analyze these tumor cell subpopulations, as they may take full advantage of growth-, survival- and immune-protective signals provided by neighbor cells. We also show a pilot study on how this approach may be applied to the analysis of cancer dormancy. Our study suggests that the detection and retrieval of DTCs in clinical studies are incomplete because they are conducted exclusively with bone marrow aspirates.
KeywordsBreast cancer Bone metastasis Disseminated tumor cells Circulating tumor cells Collagenase type 2 Cancer dormancy
Circulating tumor cells
Disseminated tumor cells
We would like to thank Aaron Muscarella for helpful suggestions. This project was supported by the Cytometry and Cell Sorting Core at Baylor College of Medicine with funding from the NIH (P30 AI036211, P30 CA125123, and S10 RR024574) and the expert assistance of Joel M. Sederstrom. X. H.-F. Z. is supported by NCI CA183878, Breast Cancer Research Foundation, US Department of Defense DAMD W81XWH-13-1-0195, Susan G. Komen CCR14298445, and McNair Medical Institute. The authors acknowledge the joint participation by Diana Helis Henry Medical Research Foundation through its direct engagement in the continuous active conduct of medical research in conjunction with Baylor College of Medicine and its “Preclinical Modeling of Metastasis and Therapy Response of TNBC” Cancer Program.
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