Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan.
Department of Chemical Engineering, University of Michigan, Ann Arbor, Michigan.
Cancer Res. 2019 Apr 15;79(8):2042-2053. doi: 10.1158/0008-5472.CAN-18-2502. Epub 2019 Feb 26.
For most cancers, metastasis is the point at which clinical treatment shifts from curative intent to extending survival. Biomaterial implants acting as a synthetic premetastatic niche recruit metastatic cancer cells and provide a survival advantage, and their use as a diagnostic platform requires assessing their relevance to disease progression. Here, we showed that scaffold-captured tumor cells (SCAF) were 30 times more metastatic to the lung than primary tumor (PT) cells, similar to cells derived from lung micrometastases (LUNG). SCAF cells were more aggressive , demonstrated higher levels of migration, invasion, and mammosphere formation, and had a greater proportion of cancer stem cells than PT. SCAF cells were highly enriched for gene expression signatures associated with metastasis and had associated genomic structural changes, including globally enhanced entropy. Collectively, our findings demonstrate that SCAF cells are distinct from PT and more closely resemble LUNG, indicating that tumor cells retrieved from scaffolds are reflective of cells at metastatic sites. SIGNIFICANCE: These findings suggest that metastatic tumor cells captured by a biomaterial scaffold may serve as a diagnostic for molecular staging of metastasis. http://cancerres.aacrjournals.org/content/canres/79/8/2042/F1.large.jpg.
对于大多数癌症来说，转移是临床治疗从治愈意图转变为延长生存的转折点。作为合成前转移龛的生物材料植入物招募转移性癌细胞，并提供生存优势，它们作为诊断平台的使用需要评估其与疾病进展的相关性。在这里，我们表明，支架捕获的肿瘤细胞（SCAF）比原发性肿瘤（PT）细胞向肺部转移的能力高 30 倍，与来自肺部微转移（LUNG）的细胞相似。SCAF 细胞更具侵袭性，表现出更高的迁移、侵袭和类器官形成能力，并且具有更多的癌症干细胞比例，高于 PT。SCAF 细胞高度富集与转移相关的基因表达特征，并且具有相关的基因组结构变化，包括全局熵增加。总的来说，我们的研究结果表明，SCAF 细胞与 PT 不同，更类似于 LUNG，这表明从支架中提取的肿瘤细胞反映了转移部位的细胞。意义：这些发现表明，生物材料支架捕获的转移性肿瘤细胞可能可作为转移分子分期的诊断工具。
