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Neoplasia ; 17(8): 625-33, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26408255

ABSTRACT

Patients with many types of malignancy commonly harbor quiescent disseminated tumor cells in bone marrow. These cells frequently resist chemotherapy and may persist for years before proliferating as recurrent metastases. To test for compounds that eliminate quiescent cancer cells, we established a new 384-well 3D spheroid model in which small numbers of cancer cells reversibly arrest in G1/G0 phase of the cell cycle when cultured with bone marrow stromal cells. Using dual-color bioluminescence imaging to selectively quantify viability of cancer and stromal cells in the same spheroid, we identified single compounds and combination treatments that preferentially eliminated quiescent breast cancer cells but not stromal cells. A treatment combination effective against malignant cells in spheroids also eliminated breast cancer cells from bone marrow in a mouse xenograft model. This research establishes a novel screening platform for therapies that selectively target quiescent tumor cells, facilitating identification of new drugs to prevent recurrent cancer.


Subject(s)
Bone Marrow Cells/pathology , Neoplasms/pathology , Spheroids, Cellular/pathology , Tumor Stem Cell Assay/methods , Animals , Antineoplastic Agents/pharmacology , Bone Marrow Cells/drug effects , Breast Neoplasms/drug therapy , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Cell Culture Techniques , Cell Cycle Checkpoints/drug effects , Cell Line, Tumor , Cell Survival/drug effects , Coculture Techniques , Drug Screening Assays, Antitumor/methods , Drug Synergism , Female , Humans , Luminescent Measurements/methods , Mice , Microscopy, Fluorescence , Neoplasms/metabolism , Spheroids, Cellular/drug effects , Xenograft Model Antitumor Assays
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