Horizontal transfer of tumor DNA to endothelial cells in vivo
Horizontal transfer of tumor DNA to endothelial cells in vivo
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DOI：
10.1038/cdd.2009.7
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发表时间：
2009-05-01
影响因子：
12.4
通讯作者：
Holmgren, L.
中科院分区：
文献类型：
--
作者：
Ehnfors, J.;Kost-Alimova, M.;Holmgren, L.
肿瘤内皮细胞长期以来被认为是基因组稳定的，因此不太可能对抗血管生成疗法产生耐药性。然而，最近的研究结果对这一概念提出了挑战。我们已经证明，DNA可以通过相邻活细胞吞噬凋亡小体在细胞间转移。通过激活p53-p21途径阻止摄入的DNA的繁殖。在这项研究中，我们研究了肿瘤DNA与抑制p53通路的基因的伴随转移是否可以克服肿瘤DNA增殖的障碍。我们的研究结果表明，成纤维细胞和内皮细胞能够获得和复制肿瘤DNA时，凋亡的肿瘤细胞含有SV 40大T抗原。对严重联合免疫缺陷小鼠异种移植肿瘤的肿瘤间质的分析显示，内皮细胞亚群含有肿瘤DNA。这些细胞在体内试验中保持形成功能性血管的能力，并同时表达肿瘤编码基因和内皮特异性基因。
Tumor endothelial cells have long been regarded as genomically stable and therefore less likely to develop resistance to antiangiogenic therapies. However, recent findings have challenged this notion. We have shown that DNA can be transferred between cells through phagocytosis of apoptotic bodies by adjacent viable cells. Propagation of the ingested DNA is prevented by the activation of the p53-p21 pathway. In this study, we examined whether concomitant transfer of tumor DNA with genes that inactivate the p53 pathway could overcome the barrier to tumor DNA propagation. Our results demonstrate that fibroblasts and endothelial cells are capable of acquiring and replicating tumor DNA when the apoptotic tumor cells contain the SV40 large T antigen. Analysis of the tumor stroma of xenotransplanted tumors in severe combined immunodeficient mice revealed that a sub-population of the endothelial cells contained tumor DNA. These cells maintained the ability to form functional vessels in an in vivo assay and concurrently express tumor-encoded and endothelial-specific genes.