7月10日,，Cancer Cell雜志報道，科學家發(fā)現(xiàn)促凋亡受體DR5可在腫瘤細胞微環(huán)境中促進凋亡,，破壞腫瘤血管,，為進一步治療腫瘤創(chuàng)造了條件。
腫瘤細胞內(nèi)的促凋亡受體DR5已被深入研究,，但其在腫瘤微環(huán)境中的功能還沒有很好地確定。本研究揭示了DR5信號在腫瘤血管內(nèi)皮細胞（ECs）中的作用,。研究發(fā)現(xiàn)在腫瘤內(nèi)皮細胞中DR5存在表達，但不在正常的組織中表達,。
給予荷瘤小鼠寡聚形式的DR5配體Apo2L/TRAIL,，可誘導腫瘤內(nèi)皮細胞的凋亡,，從而使腫瘤血管崩解,，降低腫瘤的生長。血管破壞和抗腫瘤活性,，需要DR5在腫瘤內(nèi)皮細胞表達,，但不是在腫瘤細胞本身。
這些結果確立了一個促凋亡受體激動劑治療腫瘤的新模式,。這些激動劑選擇性破壞腫瘤血管,，可為在惡性細胞中促進凋亡的激活劑提供一個替代或互補的治療策略,，從而優(yōu)化腫瘤治療效果。(生物谷bioon.com)
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.
