Colonization of distant organs by tumor cells generating circulating homotypic clusters adaptive to fluid shear stress.
Colonization of distant organs by tumor cells generating circulating homotypic clusters adaptive to fluid shear stress.
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DOI：
10.1038/s41598-021-85743-z
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发表时间：
2021-03-17
影响因子：
4.6
通讯作者：
Matsui H
中科院分区：
文献类型：
--
作者：
Maeshiro M;Shinriki S;Liu R;Nakachi Y;Komohara Y;Fujiwara Y;Ohtsubo K;Yoshida R;Iwamoto K;Nakayama H;Matsui H
一旦播散性肿瘤细胞（DTC）到达转移器官，它们就会留在那里，潜伏并成为转移的种子。然而，潜伏状态 DTC 的克隆组成仍不清楚。在这里，我们将高分辨率 DNA 条形码追踪应用于小鼠模型，该模型重现了头颈鳞状细胞癌 (HNSCC) 的转移休眠。我们发现外周血循环丰富的克隆占 DTC 的主导地位。通过对多个条形码克隆系的分析，我们确定了优先产生同型循环肿瘤细胞（CTC）簇并占主导地位的 DTC 的特定亚克隆群体。尽管在静态条件下没有显着的特征，但该群体显着产生了稳定的细胞聚集体，这些细胞聚集体在流体剪切应力（FSS）条件下以 E-钙粘蛋白依赖性方式抵抗失巢凋亡。我们来自各种癌细胞系的数据表明，聚集体构成细胞调节皮质肌动蛋白-肌球蛋白动力学的能力决定了 FSS 中聚集体的稳定性。 CTC 簇起源细胞的特征是表达富含肌动蛋白细胞骨架调节剂的 E-钙粘蛋白结合因子子集。此外，这种表达特征与 HNSCC 患者的局部区域和转移性复发相关。这些结果揭示了肿瘤细胞的生物选择，能够产生 FSS 适应性 CTC 簇，从而导致远距离定植。
Once disseminated tumor cells (DTCs) arrive at a metastatic organ, they remain there, latent, and become seeds of metastasis. However, the clonal composition of DTCs in a latent state remains unclear. Here, we applied high-resolution DNA barcode tracking to a mouse model that recapitulated the metastatic dormancy of head and neck squamous cell carcinoma (HNSCC). We found that clones abundantly circulated peripheral blood dominated DTCs. Through analyses of multiple barcoded clonal lines, we identified specific subclonal population that preferentially generated homotypic circulating tumor cell (CTC) clusters and dominated DTCs. Despite no notable features under static conditions, this population significantly generated stable cell aggregates that were resistant to anoikis under fluid shear stress (FSS) conditions in an E-cadherin-dependent manner. Our data from various cancer cell lines indicated that the ability of aggregate-constituting cells to regulate cortical actin-myosin dynamics governed the aggregates’ stability in FSS. The CTC cluster-originating cells were characterized by the expression of a subset of E-cadherin binding factors enriched with actin cytoskeleton regulators. Furthermore, this expression signature was associated with locoregional and metastatic recurrence in HNSCC patients. These results reveal a biological selection of tumor cells capable of generating FSS-adaptive CTC clusters, which leads to distant colonization.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
19
作者：
Bakir B;Chiarella AM;Pitarresi JR;Rustgi AK
通讯作者：
Rustgi AK
影响因子：
7.3
作者：
Guo Z;Neilson LJ;Zhong H;Murray PS;Zanivan S;Zaidel-Bar R
通讯作者：
Zaidel-Bar R
DOI：
10.1073/pnas.1524448113
发表时间：
2016-05-03
影响因子：
11.1
作者：
Au, Sam H.;Storey, Brian D.;Toner, Mehmet
通讯作者：
Toner, Mehmet
DOI：
10.1073/pnas.1508541113
发表时间：
2016-02-16
影响因子：
11.1
作者：
Cheung, Kevin J.;Padmanaban, Veena;Ewald, Andrew J.
通讯作者：
Ewald, Andrew J.