一种用于无标记物理捕获循环肿瘤细胞簇的微流控装置。
A microfluidic device for label-free, physical capture of circulating tumor cell clusters.
作者信息
Sarioglu A Fatih, Aceto Nicola, Kojic Nikola, Donaldson Maria C, Zeinali Mahnaz, Hamza Bashar, Engstrom Amanda, Zhu Huili, Sundaresan Tilak K, Miyamoto David T, Luo Xi, Bardia Aditya, Wittner Ben S, Ramaswamy Sridhar, Shioda Toshi, Ting David T, Stott Shannon L, Kapur Ravi, Maheswaran Shyamala, Haber Daniel A, Toner Mehmet
机构信息
1] Center for Engineering in Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. [2] Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. [3] Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
1] Cancer Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA. [2] Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
出版信息
Nat Methods. 2015 Jul;12(7):685-91. doi: 10.1038/nmeth.3404. Epub 2015 May 18.
Cancer cells metastasize through the bloodstream either as single migratory circulating tumor cells (CTCs) or as multicellular groupings (CTC clusters). Existing technologies for CTC enrichment are designed to isolate single CTCs, and although CTC clusters are detectable in some cases, their true prevalence and significance remain to be determined. Here we developed a microchip technology (the Cluster-Chip) to capture CTC clusters independently of tumor-specific markers from unprocessed blood. CTC clusters are isolated through specialized bifurcating traps under low-shear stress conditions that preserve their integrity, and even two-cell clusters are captured efficiently. Using the Cluster-Chip, we identified CTC clusters in 30-40% of patients with metastatic breast or prostate cancer or with melanoma. RNA sequencing of CTC clusters confirmed their tumor origin and identified tissue-derived macrophages within the clusters. Efficient capture of CTC clusters will enable the detailed characterization of their biological properties and role in metastasis.
癌细胞通过血液循环转移，要么是单个迁移的循环肿瘤细胞（CTC），要么是多细胞聚集体（CTC簇）。现有的CTC富集技术旨在分离单个CTC，尽管在某些情况下可以检测到CTC簇，但其真实发生率和意义仍有待确定。在这里，我们开发了一种微芯片技术（Cluster-Chip），用于从未经处理的血液中独立于肿瘤特异性标志物捕获CTC簇。CTC簇通过专门的分叉陷阱在低剪切应力条件下分离，以保持其完整性，甚至两个细胞的簇也能被有效捕获。使用Cluster-Chip，我们在30%-40%的转移性乳腺癌、前列腺癌或黑色素瘤患者中鉴定出了CTC簇。对CTC簇的RNA测序证实了它们的肿瘤起源，并在簇内鉴定出了组织来源的巨噬细胞。有效捕获CTC簇将有助于详细表征其生物学特性及其在转移中的作用。
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