Pancreatic Cancer Metastases Harbor Evidence of Polyclonality.
Pancreatic Cancer Metastases Harbor Evidence of Polyclonality.
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DOI：
10.1158/2159-8290.cd-15-0120
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发表时间：
2015-10
期刊：
影响因子：
28.2
通讯作者：
Stanger BZ
中科院分区：
文献类型：
--
作者：
Maddipati R;Stanger BZ
对癌症基因组的研究表明，肿瘤由多个具有不同遗传和表型特性的亚克隆组成。然而，关于转移是如何从这些亚克隆产生和演变的，人们知之甚少。为了了解驱动转移的细胞动力学，我们在胰腺癌的本土小鼠模型中使用了多色谱系追踪技术。在这里，我们报告了前驱病变表现出显著的克隆性异质性，但这种多样性在癌前进展过程中减少。此外，我们提出的证据表明，很大一部分转移瘤是由不同的肿瘤亚克隆多克隆种植的。最后，我们发现转移生长过程中的克隆性--导致单克隆性或多克隆性扩张--根据转移侵袭部位的不同而不同。这些结果为了解肿瘤进化的细胞动力学提供了一个前所未有的窗口，并表明肿瘤亚群之间的异型相互作用有助于天然肿瘤的转移进展。
Studies of the cancer genome have demonstrated that tumors are comprised of multiple sub-clones with varied genetic and phenotypic properties. However, little is known about how metastases arise and evolve from these sub-clones. To understand the cellular dynamics that drive metastasis, we used multi-color lineage tracing technology in an autochthonous mouse model of pancreatic cancer. Here, we report that precursor lesions exhibit significant clonal heterogeneity but that this diversity decreases during pre-malignant progression. Furthermore, we present evidence that a significant fraction of metastases are polyclonally seeded by distinct tumor sub-clones. Finally, we show that clonality during metastatic growth – leading to either monoclonal or polyclonal expansion – differs based on the site of metastatic invasion. These results provide an unprecedented window into the cellular dynamics of tumor evolution and suggest that heterotypic interactions between tumor subpopulations contribute to metastatic progression in native tumors.