Journal
SCIENTIFIC REPORTS
Volume 8, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-018-32653-2
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Funding
- NCI/NIH Cancer Center Support Grant [5P30 CA68485-19]
- Vanderbilt Mouse Metabolic Phenotyping Center Grant [2 U24 DK059637-16]
- Vanderbilt Ingram Cancer Center [P30 CA68485]
- Vanderbilt Digestive Disease Research Center [DK058404]
- NIH [R00CA194198, P30 CA068485]
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Breast cancer cells frequently home to the bone, but the mechanisms controlling tumor colonization of the bone marrow remain unclear. We report significant enrichment of bone-disseminated estrogen receptor positive human MCF7 cells by 17 beta-estradiol (E2) following intracardiac inoculation. Using flow cytometric and quantitative PCR approaches, tumor cells were detected in >80% of MCF7 tumor-inoculated mice, regardless of E2, suggesting that E2 is not required for MCF7 dissemination to the bone marrow. Furthermore, we propose two additional models in which to study prolonged latency periods by bone-disseminated tumor cells: murine D2.0R and human SUM159 breast carcinoma cells. Tumor cells were detected in bone marrow of up to 100% of D2.0R and SUM159-inoculated mice depending on the detection method. These findings establish novel models of bone colonization in which to study mechanisms underlying tumor cell seeding to the marrow and prolonged latency, and provide highly sensitive methods to detect these rare events.
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