Program in Cancer Biology, Vanderbilt University, Nashville, TN, 37232, USA.
Vanderbilt Center for Bone Biology, Department of Medicine, Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
Sci Rep. 2018 Sep 24;8(1):14299. doi: 10.1038/s41598-018-32653-2.
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 β-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.
乳腺癌细胞经常转移到骨骼，但控制肿瘤向骨髓定植的机制仍不清楚。我们报告说，在心脏内接种后，17β-雌二醇（E2）显著富集了骨播散的雌激素受体阳性人 MCF7 细胞。通过流式细胞术和定量 PCR 方法，在>80%的 MCF7 肿瘤接种小鼠中检测到肿瘤细胞，无论是否存在 E2，这表明 E2 对于 MCF7 向骨髓的扩散不是必需的。此外，我们提出了另外两种模型，通过骨播散的肿瘤细胞来研究延长潜伏期：鼠 D2.0R 和人 SUM159 乳腺癌细胞。根据检测方法，高达 100%的 D2.0R 和 SUM159 接种小鼠的骨髓中检测到肿瘤细胞。这些发现建立了新的骨定植模型，用于研究肿瘤细胞向骨髓定植和延长潜伏期的机制，并提供了高度敏感的方法来检测这些罕见事件。
