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.
| Original language | English |
|---|---|
| Pages (from-to) | 625-633 |
| Number of pages | 9 |
| Journal | Neoplasia |
| Volume | 17 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - 2015 |
| Externally published | Yes |
Bibliographical note
Funding Information:This work was supported by United States National Institutes of Health grants R01CA170198 and 1S10RR028819 . SPC was supported by a NSF predoctoral fellowship F031543 and the Advanced Proteome Informatics of Cancer Training Grant # T32 CA140044 . We thank Judith Leopold for her helpful discussion of this work. We thank Aaron Robida and the University of Michigan Flow Cytometry Core for help optimizing analysis of bone marrow samples.
Publisher Copyright:
© 2015 The Authors.
ASJC Scopus Subject Areas
- Cancer Research
