Malignant subclone drives metastasis of genetically and phenotypically heterogenous cell clusters through fibrotic niche generation.
Malignant subclone drives metastasis of genetically and phenotypically heterogenous cell clusters through fibrotic niche generation.
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DOI：
10.1038/s41467-021-21160-0
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发表时间：
2021-02-08
影响因子：
16.6
通讯作者：
Oshima M
中科院分区：
文献类型：
--
作者：
Kok SY;Oshima H;Takahashi K;Nakayama M;Murakami K;Ueda HR;Miyazono K;Oshima M
最近提出了多克隆转移的概念，其中肿瘤细胞簇从原发部位脱落并扩散。然而，在这种多克隆机制中驱动突变的参与还没有完全理解。在这里，我们表明，非转移性AP细胞转移到肝脏与转移性AKTP细胞共移植到脾脏后。此外，AKTP细胞耗尽后的发展转移的结果在剩余的AP细胞的持续增殖，表明AKTP细胞在多克隆转移的早期步骤中的作用。重要的是，AKTP细胞而不是AP细胞在窦状隙中停滞时诱导纤维化小生境产生，并且这种纤维化微环境促进AP细胞的定殖。这些结果表明，非转移性细胞可以通过多克隆转移机制，利用恶性细胞诱导的纤维化龛转移。因此，靶向纤维化小生境是阻止多克隆转移的有效策略。癌细胞簇通过多克隆方式转移到远处器官。在这里，作者表明，恶性亚克隆通过肝星状细胞活化诱导肝脏中的纤维化小生境产生，支持非转移性细胞的存活和定殖以发展多克隆转移。
A concept of polyclonal metastasis has recently been proposed, wherein tumor cell clusters break off from the primary site and are disseminated. However, the involvement of driver mutations in such polyclonal mechanism is not fully understood. Here, we show that non-metastatic AP cells metastasize to the liver with metastatic AKTP cells after co-transplantation to the spleen. Furthermore, AKTP cell depletion after the development of metastases results in the continuous proliferation of the remaining AP cells, indicating a role of AKTP cells in the early step of polyclonal metastasis. Importantly, AKTP cells, but not AP cells, induce fibrotic niche generation when arrested in the sinusoid, and such fibrotic microenvironment promotes the colonization of AP cells. These results indicate that non-metastatic cells can metastasize via the polyclonal metastasis mechanism using the fibrotic niche induced by malignant cells. Thus, targeting the fibrotic niche is an effective strategy for halting polyclonal metastasis. Cancer cell clusters metastasize to distant organ by polyclonal manner. Here, the authors show that malignant subclone induces fibrotic niche generation in the liver by hepatic stellate cell activation, supporting survival and colonization of non-metastatic cells to develop polyclonal metastasis.
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影响因子：
1.5
作者：
Chytil, A;Magnuson, MA;Moses, HL
通讯作者：
Moses, HL
DOI：
10.1038/nrc.2017.126
发表时间：
2018-04
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
Hunter KW;Amin R;Deasy S;Ha NH;Wakefield L
通讯作者：
Wakefield L
影响因子：
28.2
作者：
Liu X;Taftaf R;Kawaguchi M;Chang YF;Chen W;Entenberg D;Zhang Y;Gerratana L;Huang S;Patel DB;Tsui E;Adorno-Cruz V;Chirieleison SM;Cao Y;Harney AS;Patel S;Patsialou A;Shen Y;Avril S;Gilmore HL;Lathia JD;Abbott DW;Cristofanilli M;Condeelis JS;Liu H
通讯作者：
Liu H
影响因子：
21.3
作者：
Costa-Silva B;Aiello NM;Ocean AJ;Singh S;Zhang H;Thakur BK;Becker A;Hoshino A;Mark MT;Molina H;Xiang J;Zhang T;Theilen TM;García-Santos G;Williams C;Ararso Y;Huang Y;Rodrigues G;Shen TL;Labori KJ;Lothe IM;Kure EH;Hernandez J;Doussot A;Ebbesen SH;Grandgenett PM;Hollingsworth MA;Jain M;Mallya K;Batra SK;Jarnagin WR;Schwartz RE;Matei I;Peinado H;Stanger BZ;Bromberg J;Lyden D
通讯作者：
Lyden D
影响因子：
28.2
作者：
Maddipati R;Stanger BZ
通讯作者：
Stanger BZ