Yale Institute of Systems Biology, Yale University, West Haven, CT, USA.
Department of Biomedical Engineering, Yale University, New Haven, CT, USA.
Nat Ecol Evol. 2019 Dec;3(12):1743-1753. doi: 10.1038/s41559-019-1046-4. Epub 2019 Nov 25.
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.
在哺乳动物中，胎盘浸润与恶性肿瘤的易感性相关。胎盘浸润性更强的动物（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“进化程度可入侵性假说”，该假说提出基质组织的可入侵性进化会同时影响胎盘和癌症的侵袭。我们使用体外模型提供了这方面的证据。我们发现牛子宫内膜和皮肤成纤维细胞比人源成纤维细胞更能抵抗入侵。基因表达谱分析确定了在人类成纤维细胞中高表达而在牛源成纤维细胞中低表达的基因。在人源成纤维细胞中敲低其中一部分基因会导致对癌细胞侵袭的抵抗力更强。确定基质可入侵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。
