Cancer Cell:促凋亡受体DR5破坏肿瘤血管

7月10日，Cancer Cell杂志报道，科学家发现促凋亡受体DR5可在肿瘤细胞微环境中促进凋亡，破坏肿瘤血管，为进一步治疗肿瘤创造了条件。

肿瘤细胞内的促凋亡受体DR5已被深入研究，但其在肿瘤微环境中的功能还没有很好地确定。本研究揭示了DR5信号在肿瘤血管内皮细胞（ECs）中的作用。研究发现在肿瘤内皮细胞中DR5存在表达，但不在正常的组织中表达。

给予荷瘤小鼠寡聚形式的DR5配体Apo2L/TRAIL，可诱导肿瘤内皮细胞的凋亡，从而使肿瘤血管崩解，降低肿瘤的生长。血管破坏和抗肿瘤活性，需要DR5在肿瘤内皮细胞表达，但不是在肿瘤细胞本身。

这些结果确立了一个促凋亡受体激动剂治疗肿瘤的新模式。这些激动剂选择性破坏肿瘤血管，可为在恶性细胞中促进凋亡的激活剂提供一个替代或互补的治疗策略，从而优化肿瘤治疗效果。

doi:10.1016/j.cell.2011.10.017
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Proapoptotic Activation of Death Receptor 5 on Tumor Endothelial Cells Disrupts the Vasculature and Reduces Tumor Growth

Nicholas S. Wilson, Annie Yang, Becky Yang, Suzana Couto, Howard Stern, Alvin Gogineni, Robert Pitti, Scot Marsters, Robby M. Weimer, Mallika Singh, Avi Ashkenazi

The proapoptotic death receptor DR5 has been studied extensively in cancer cells, but its action in the tumor microenvironment is not well defined. Here, we uncover a role for DR5 signaling in tumor endothelial cells (ECs). We detected DR5 expression in ECs within tumors but not normal tissues. Treatment of tumor-bearing mice with an oligomeric form of the DR5 ligand Apo2L/TRAIL induced apoptosis in tumor ECs, collapsing blood vessels and reducing tumor growth: Vascular disruption and antitumor activity required DR5 expression on tumor ECs but not malignant cells. These results establish a therapeutic paradigm for proapoptotic receptor agonists as selective tumor vascular disruption agents, providing an alternative, perhaps complementary, strategy to their use as activators of apoptosis in malignant cells.