Multicolor lineage tracing reveals clonal architecture and dynamics in colon cancer.
Multicolor lineage tracing reveals clonal architecture and dynamics in colon cancer.
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DOI：
10.1038/s41467-017-00976-9
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发表时间：
2017-11-10
影响因子：
16.6
通讯作者：
Horst D
中科院分区：
文献类型：
--
作者：
Lamprecht S;Schmidt EM;Blaj C;Hermeking H;Jung A;Kirchner T;Horst D
结肠癌由表型不同的肿瘤细胞亚群组成，这些亚群具有不同的假定干细胞和分化抗原的表达。而在正常结肠粘膜中，克隆再繁殖是沿着从隐窝底部到隐窝顶端的分化梯度进行的，结肠癌的克隆构筑和肿瘤细胞亚群与克隆生长的相关性尚不清楚。在反映原发结肠癌结构的异种结肠癌移植瘤中使用多色谱系示踪方法，我们在这里证明克隆性生长主要由位于肿瘤前沿的肿瘤细胞驱动，克隆轴形成朝向肿瘤中心。虽然我们的发现与肿瘤干细胞模型中的谱系生长是一致的，但它们表明，在结直肠癌中，肿瘤细胞的位置对克隆性生长可能比肿瘤细胞表型更重要。结肠癌的克隆性结构和肿瘤细胞亚群与克隆性生长的相关性还知之甚少。在这里，作者描述了人类结肠癌的克隆结构和动力学，在结肠癌异种移植中使用了多色谱系追踪方法。
Colon cancers are composed of phenotypically heterogeneous tumor cell subpopulations with variable expression of putative stem cell and differentiation antigens. While in normal colonic mucosa, clonal repopulation occurs along differentiation gradients from crypt base toward crypt apex, the clonal architecture of colon cancer and the relevance of tumor cell subpopulations for clonal outgrowth are poorly understood. Using a multicolor lineage tracing approach in colon cancer xenografts that reflect primary colon cancer architecture, we here demonstrate that clonal outgrowth is mainly driven by tumor cells located at the leading tumor edge with clonal axis formation toward the tumor center. While our findings are compatible with lineage outgrowth in a cancer stem cell model, they suggest that in colorectal cancer tumor cell position may be more important for clonal outgrowth than tumor cell phenotype. The clonal architecture of colon cancer and the relevance of tumor cell subpopulations for clonal outgrowth are poorly understood. Here, the authors describe the clonal architecture and dynamics in human colon cancer by using a multicolor lineage tracing approach in colon cancer xenografts.
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影响因子：
11.2
作者：
Horst D;Chen J;Morikawa T;Ogino S;Kirchner T;Shivdasani RA
通讯作者：
Shivdasani RA
影响因子：
64.8
作者：
Greaves, Mel;Maley, Carlo C.
通讯作者：
Maley, Carlo C.
影响因子：
5.2
作者：
Zomer, Anoek;Ellenbroek, Saskia Inge Johanna;Ritsma, Laila;Beerling, Evelyne;Vrisekoop, Nienke;Van Rheenen, Jacco
通讯作者：
Van Rheenen, Jacco
DOI：
10.1073/pnas.1220353110
发表时间：
2013-07-02
影响因子：
11.1
作者：
Humphries, Adam;Cereser, Biancastella;Graham, Trevor A.
通讯作者：
Graham, Trevor A.
影响因子：
21.3
作者：
Vermeulen, Louis;Melo, Felipe De Sousa E.;Medema, Jan Paul
通讯作者：
Medema, Jan Paul