Transient commensal clonal interactions can drive tumor metastasis.
Transient commensal clonal interactions can drive tumor metastasis.
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短暂的细胞克隆相互作用可以驱动肿瘤转移。
DOI：
10.1038/s41467-020-19584-1
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发表时间：
2020-11-16
影响因子：
16.6
通讯作者：
Brugge JS
中科院分区：
文献类型：
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作者：
Naffar-Abu Amara S;Kuiken HJ;Selfors LM;Butler T;Leung ML;Leung CT;Kuhn EP;Kolarova T;Hage C;Ganesh K;Panayiotou R;Foster R;Rueda BR;Aktipis A;Spellman P;Ince TA;Xiu J;Oberley M;Gatalica Z;Navin N;Mills GB;Bronson RT;Brugge JS
肿瘤细胞之间的功能异质性和串扰的程度和重要性知之甚少。在这里，我们描述了从患者来源的卵巢透明细胞癌模型，形成恶性腹水和实体腹膜肿瘤后，腹腔移植小鼠的克隆群体的一代。克隆群体用分泌的Gaussia荧光素酶工程化以监测肿瘤生长动力学，并用独特的DNA条形码标记以在肿瘤进展期间跟踪它们在多克隆混合物中的命运。只有一个克隆，CL31，生长健壮，产生专门的恶性腹水。然而，多克隆混合物形成大的固体腹膜转移，几乎完全由CL31填充，这表明瞬时合作的克隆间相互作用足以促进CL31的转移。CL31独特地具有ERBB2扩增，并且其在克隆混合物中获得的转移活性依赖于瞬时暴露于双调蛋白，双调蛋白仅由非致瘤性克隆分泌。双调蛋白增强CL31间皮细胞清除，这是转移的先决条件。这些发现表明，短暂的，表面上无害的肿瘤亚群可以通过“打了就跑”的肿瘤相互作用促进转移。肿瘤细胞之间的协同作用可能对转移具有重要意义。在这里，作者研究了卵巢癌细胞克隆群体之间相互作用的时空性质，发现瞬时相互作用细胞可以通过细胞相互作用促进转移。
The extent and importance of functional heterogeneity and crosstalk between tumor cells is poorly understood. Here, we describe the generation of clonal populations from a patient-derived ovarian clear cell carcinoma model which forms malignant ascites and solid peritoneal tumors upon intraperitoneal transplantation in mice. The clonal populations are engineered with secreted Gaussia luciferase to monitor tumor growth dynamics and tagged with a unique DNA barcode to track their fate in multiclonal mixtures during tumor progression. Only one clone, CL31, grows robustly, generating exclusively malignant ascites. However, multiclonal mixtures form large solid peritoneal metastases, populated almost entirely by CL31, suggesting that transient cooperative interclonal interactions are sufficient to promote metastasis of CL31. CL31 uniquely harbors ERBB2 amplification, and its acquired metastatic activity in clonal mixtures is dependent on transient exposure to amphiregulin, which is exclusively secreted by non-tumorigenic clones. Amphiregulin enhances CL31 mesothelial clearance, a prerequisite for metastasis. These findings demonstrate that transient, ostensibly innocuous tumor subpopulations can promote metastases via “hit-and-run” commensal interactions. Cooperative interactions among tumor cells may have important implications for metastasis. Here, the authors examined the spatio-temporal nature of interactions among clonal populations of ovarian carcinoma cells and found that transient interactions cells can promote metastases via commensal interactions.
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影响因子：
10.5
作者：
Inda, Maria-del-Mar;Bonavia, Rudy;Furnari, Frank
通讯作者：
Furnari, Frank
影响因子：
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作者：
Hayashida T;Jinno H;Kitagawa Y;Kitajima M
通讯作者：
Kitajima M
DOI：
10.1073/pnas.0606053103
发表时间：
2006-09-05
影响因子：
11.1
作者：
Axelrod, Robert;Axelrod, David E.;Pienta, Kenneth J.
通讯作者：
Pienta, Kenneth J.
影响因子：
6.4
作者：
Koopman, Timco;van der Vegt, Bert;Hollema, Harry
通讯作者：
Hollema, Harry
影响因子：
64.8
作者：
通讯作者：
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