Evolution of placental invasion and cancer metastasis are causally linked
Evolution of placental invasion and cancer metastasis are causally linked
复制标题
DOI：
10.1038/s41559-019-1046-4
复制
发表时间：
2019-12-01
影响因子：
16.8
通讯作者：
Wagner, Gunter P.
中科院分区：
文献类型：
--
作者：
Kshitiz;Afzal, Junaid;Wagner, Gunter P.
在哺乳动物中，胎盘的侵袭与易患恶性肿瘤有关。有更多侵入性胎盘的动物（例如人类）更容易患恶性肿瘤。为了解释这种相关性，我们提出了“不可侵入性的进化水平”假说，提出基质组织不可侵入性的进化影响胎盘和癌症的侵袭。我们使用体外模型为这一点提供证据。我们发现牛子宫内膜和皮肤成纤维细胞比它们的人类对应物更能抵抗入侵。基因表达谱鉴定出在人类成纤维细胞中高表达的基因，而在牛成纤维细胞中不表达。在人类成纤维细胞中敲除它们的一个子集可以增强对癌细胞入侵的抵抗力。确定基质侵袭性的进化决定因素可以为开发合理的抗转移治疗提供重要的见解。
Among mammals, placental invasion is correlated with vulnerability to malignancy. Animals with more invasive placentation (for example, humans) are more vulnerable to malignancy. To explain this correlation, we propose the hypothesis of 'Evolved Levels of Invasibility' proposing that the evolution of invasibility of stromal tissue affects both placental and cancer invasion. We provide evidence for this using an in vitro model. We find that bovine endometrial and skin fibroblasts are more resistant to invasion than are their human counterparts. Gene expression profiling identified genes with high expression in human but not in bovine fibroblasts. Knocking down a subset of them in human fibroblasts leads to stronger resistance to cancer cell invasion. Identifying the evolutionary determinants of stromal invasibility can provide important insights to develop rational antimetastatic therapeutics.